Systemic irradiation for selected stage IV and recurrent pediatric solid tumors: method, toxicity, and preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wharam, M.D.; Kaizer, H.; Leventhal, B.G.

1980-02-01

Eight patients with advanced pediatric solid tumors received either sequential upper and lower half-body irradiation (HBI) (7.5 rad/min to 500 rad total) or total body irradiation (TBI) (7.5 rad/min to 800 rad total) as part of two multimodality treatment regimens. All patients received combination chemotherapy; drugs were determined by the tumor type. The TBI regimen was selected for two patients who had progression of disease with conventional chemotherapy and for two patients with stage IV neuroblastoma. This intensive regimen consisted of bone marrow harvesting, followed by local radiation to gross disease, marrow-ablative chemotherapy, TBI, and re-infusion of the cryopreserved autologousmore » marrow. Significant acute toxicity was followed by hematologic reconstitution in each patient within seven weeks. At this writing, two patients survived, one of whom is disease free two and one half years without maintenance chemotherapy. A less intensive, outpatient regimen was selected for four patients; three had a complete or good partial response to chemotherapy. The fourth patient had tumor-involved bone marrow not responsive to chemotherapy and was therefore ineligible for marrow cryopreservation and TBI. Each of these four patients received HBI after chemotherapy and local radiation to the primary and/or metastatic sites. Acute toxicity was limited to nausea and vomiting. Significant leukopenia and thrombocytopenia occurred in three patients. All four patients were alive 10 to 26 months post HBI. This pilot study demonstrates that chemotherapy can be integrated with local fractionated radiation, and systemic radiation given as HBI or TBI with acceptable toxicity; sufficient bone marrow stem cells can be harvested after conventional chemotherapy and then cryopreserved to permit hematologic reconstitution of the patient who receives marrow ablative therapy.« less

Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note.

PubMed

Benthien, Jan P; Behrens, Peter

2013-11-01

The potential of subchondral mesenchymal stem cell stimulation (MSS) for cartilage repair has led to the widespread use of microfracture as a first line treatment for full thickness articular cartilage defects. Recent focus on the effects of subchondral bone during cartilage injury and repair has expanded the understanding of the strengths and limitations in MSS and opened new pathways for potential improvement. Comparative studies have shown that bone marrow access has positive implications for pluripotential cell recruitment, repair quality and quantity, i.e. deeper channels elicited better cartilage fill, more hyaline cartilage character with higher type II collagen content and lower type I collagen content compared to shallow marrow access. A subchondral needling procedure using standardised and thin subchondral perforations deep into the subarticular bone marrow making the MSS more consistent with the latest developments in subchondral cartilage remodelling is proposed. As this is a novel method clinical studies have been initiated to evaluate the procedure especially compared to microfracturing. However, the first case studies and follow-ups indicate that specific drills facilitate reaching the subchondral bone marrow while the needle size makes perforation of the subchondral bone easier and more predictable. Clinical results of the first group of patients seem to compare well to microfracturing. The authors suggest a new method for a standardised procedure using a new perforating device. Advances in MSS by subchondral bone marrow perforation are discussed. It remains to be determined by clinical studies how this method compares to microfracturing. The subchondral needling offers the surgeon and the investigator a method that facilitates comparison studies because of its defined depth of subchondral penetration and needle size.

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

PubMed Central

Green, Danielle E.; Rubin, Clinton T.

2014-01-01

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

Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

PubMed

Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

2015-07-01

The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisse, N; Jeraj, R

Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton,more » quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUV mean, SUV max, and SUV CV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUV mean, SUV max, and SUV CV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUV mean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUV max correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT PET. These results provide a baseline characterization against which proliferative activity of abnormal marrow can be compared.« less

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies.

PubMed

Blume, K G; Forman, S J

1992-12-01

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.

Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation.

PubMed Central

Papadimitriou, A; Urena, M; Hamill, G; Stanhope, R; Leiper, A D

1991-01-01

Growth hormone was given to 13 children (nine boys, four girls) with acute leukaemia who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation. Mean age at total body irradiation and bone marrow transplantation was 9.0 years (range 3.7-15.8). Endocrinological investigation was carried out at a mean of 2.0 years (range 0.4-4.0) after bone marrow transplantation. Peak serum growth hormone responses to hypoglycaemia were less than 10.0 micrograms/l (less than 20.0 mU/l) in 10, 10.5 micrograms/l (21.0 mU/l) in one, greater than 16.0 micrograms/l (greater than 32.0 mU/l) in two patients. Mean age of the patients at the start of growth hormone treatment was 12.2 years (range 5.8-18.2). The mean time between total body irradiation and bone marrow transplantation and the start of growth hormone treatment was 3.2 years (range, 1.1-5.0). Height velocity SD score (SD) increased from a mean pretreatment value of -1.27 (0.65) to + 0.22 (0.81) in the first year, +0.16 (1.11) in the second year, and +0.42 (0.71) in the third year of treatment. Height SD score (SD) changed only slightly from -1.52 (0.42) to -1.50 (0.47) in the first year, to -1.50 (0.46) in the second year, and -1.74 (0.92) in the third year. Measurement of segmental proportions showed no significant increase in subischial leg length from -0.87 (0.67) to -0.63 (0.65) in the first year, to -0.58 (0.70) in the second year, and -0.80 (1.14) in the third year of treatment. Our data indicate that children who have undergone total body irradiation and bone marrow transplantation respond to treatment with growth hormone in either of two dose regimens, with an increase in height velocity that is adequate to restore a normal growth rate but not to 'catch up', and that total body irradiation impairs not only spinal but also leg growth, possibly by a direct effect of irradiation on the epiphyses and soft tissues. PMID:2053788

Growth of erythroid burst-forming units (BFU-E) in cultures of canine bone marrow and peripheral blood cells: effect of serum from irradiated dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreja, L.; Baltschukat, K.; Nothdurft, W.

1988-08-01

Erythroid burst-forming units (BFU-E) from canine bone marrow and peripheral blood could be grown in methylcellulose in the presence of an appropriate batch of fetal calf serum (FCS), transferrin, and erythropoietin (Epo). However, improved colony formation (size and number of bursts) was obtained when serum from total body irradiated dogs was present in the culture. This serum, obtained from dogs at day 9 after total body irradiation with a dose of 3.9 Gy, reduced markedly the Epo requirement of BFU-E. Furthermore, it allowed the omission of FCS from the culture medium if cholesterol and bovine serum albumin (BSA) were usedmore » as FCS substitutes. BFU-E concentrations were found to be rather different in the peripheral blood and in bone marrow samples from different sites (i.e., iliac crest, sternum, and humerus) of normal beagles. The studies further show that canine bone marrow BFU-E can be cryopreserved in liquid nitrogen.« less

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

PubMed Central

2013-01-01

Introduction The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. Methods A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Results Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. Conclusions We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS. PMID:23497755

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L J; Vellekoop, L; Thomson, S; Stewart, D; Hester, J P; McCredie, K B

1979-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L; Vellekoop, L; Thomson, S; Stewart, D; McCredie, K B

1980-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%) when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Yin, Y

Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) andmore » 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer.« less

[Plasma and tissue lipids in rats after a flight on the Kosmos-1129 biosatellite].

PubMed

Ahlers, J; Tigranian, R A; D'jatelinka, J; Smajda, B; Toropila, M

1982-01-01

Concentrations of triglycerides, total cholesterol, lipid phosphorus and nonesterified fatty acids were measured in blood plasma, liver, thymus, bone marrow and adipose tissues of rats flown for 18.5 days onboard the biosatellite Cosmos-1129. This exposure was accompanied by increases in lipomobilization, content of total cholesterol and lipid phosphorus in plasma, and triglycerides in the thymus and bone marrow. The postflight exposure to repeated stresses demonstrated changes in the lipid content in all animal groups, especially in flight rats.

Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation

PubMed Central

Hisatomi, Toshio; Sonoda, Koh‐hei; Ishikawa, Fumihiko; Qiao, Hong; Nakamura, Takahiro; Fukata, Mitsuhiro; Nakazawa, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi‐Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

2007-01-01

Aims To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Methods Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild‐type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. Results GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. Conclusion We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU. PMID:17035278

Marrow grafts from HLA-identical siblings for severe aplastic anemia: does limiting the number of transplanted marrow cells reduce the risk of chronic GvHD?

PubMed

Gallo, S; Woolfrey, A E; Burroughs, L M; Storer, B E; Flowers, M E D; Hari, P; Pulsipher, M A; Heimfeld, S; Kiem, H-P; Sandmaier, B M; Storb, R

2016-12-01

A total of 21 patients with severe aplastic anemia (SAA) underwent marrow transplantation from HLA-identical siblings following a standard conditioning regimen with cyclophosphamide (50 mg/kg/day × 4 days) and horse antithymocyte globulin (30 mg/kg/day × 3 days). Post-grafting immunosuppression consisted of a short course of methotrexate (MTX) combined with cyclosporine (CSP). The transplant protocol tested the hypothesis that the incidence of chronic GvHD could be reduced by limiting the marrow grafts to ⩽2.5 × 10 8 nucleated marrow cells/kg. None of the patients rejected the graft, all had sustained engraftment and all are surviving at a median of 4 (range 1-8) years after transplantation. Chronic GvHD developed in 16% of patients given ⩽2.5 × 10 8 nucleated marrow cells/kg. Post-grafting immunosuppression has been discontinued in 20 of the 21 patients. In conclusion, limiting the number of transplanted marrow cells may have resulted in minimal improvement in the incidence and severity of chronic GvHD.

A study of bone marrow and subcutaneous fatty acid composition in subjects of varying bone mineral density.

PubMed

Griffith, James F; Yeung, David K W; Ahuja, Anil T; Choy, Carol W Y; Mei, Wong Yin; Lam, Sherlock S L; Lam, T P; Chen, Zhen-Yu; Leung, Ping C

2009-06-01

Osteoporosis is associated with an increase in marrow fat. Fats, particularly polyunsaturated fats, either in co-cultures or diet, have been shown to significantly influence bone remodeling. Whether the increase in marrow fat seen in osteoporosis is also associated with a change in fatty acid composition is not known. This study was undertaken to investigate the fatty acid composition in subjects of varying bone mineral density (BMD). Samples of marrow fat and subcutaneous fat from 126 subjects (98 females, 34 males, mean age 69.7+/-10.5 years) undergoing orthopedic surgery were analyzed for fatty acid composition by gas chromatography. These results were correlated with BMD assessed by DXA. A total of 22 fatty acids were identified in marrow and subcutaneous fat. Significant differences in fatty acid composition existed between marrow and subcutaneous fat as well as between marrow fat samples obtained from the proximal femur and proximal tibia. Other than cis-7-hexadecenoic acid [C16:1 (n=9)] and docosanoic acid [C22:0], no difference in marrow fatty acid composition was evident between subject groups of varying BMD (normal, low bone mass, and osteoporosis). In conclusion, there exists a wide range of individual fatty acids in marrow fat. Marrow fatty acid composition differs from that of subcutaneous fat and varies between predominantly erythropoetic and fatty marrow sites. Other than cis-7-hexadecenoic acid [C16:1 (n=9)] and docosanoic acid [C22:0], no difference in marrow fatty acid composition was evident between subjects of varying BMD.

Concentrations and potential health hazards of polycyclic aromatic hydrocarbon in shallow groundwater of a metal smelting area in Southeastern China.

PubMed

Wu, Chunfa; Zhu, Hao; Luo, Yongming; Wang, Jun

2016-11-01

A total of 20 shallow groundwater samples were collected from a metal smelting area in southeastern China to determine the concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs), calculate their toxic equivalents (TEQs) to benzo[a]pyrene (BaP), and estimate the carcinogenic risk of drinking the shallow groundwater. The total concentrations of the 16PAHs (∑PAHs) in the shallow groundwater ranged from 9.62 to 1663.93ngL(-1), with a mean value of 312.63ngL(-1), and the total concentrations of the 7 potentially carcinogenic PAHs (∑PAHC7) ranged from 3.11 to 33.60ngL(-1), with a mean value of 9.61ngL(-1). Naphthalene and BaP, were the dominant PAH species and potentially carcinogenic PAH species in the shallow groundwater of the study area, and they account for 89.97% of ∑PAHs and 82.62% of ∑PAHC7, respectively. High molecular weight-PAHs (HM-PAHs) accounted for a relatively high proportion in the majority of shallow groundwater samples with lower concentrations of ΣPAHs, indicated that HM-PAHs were mainly from historical residues. The TEQs to BaP of the 16PAHs in the 20 shallow groundwater samples varied greatly from 2.55 to 32.73ngL(-1), with a mean value of 8.61ngL(-1), and BaP was the dominant contributor. The total carcinogenic risk levels caused by the 16PAHs in the shallow groundwater in majority of the area were found to be higher than the limit set by the US EPA, posing a potentially serious health risk to those who depend on shallow groundwater for drinking water. Copyright © 2016. Published by Elsevier B.V.

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

PubMed Central

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model.

PubMed

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Yeap, Swee Keong; Abdul Samad, Nozlena; Andas, Reena Joys; Muhammad Nadzri, Nabilah; Anasamy, Theebaa; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Ionizing radiation stimulates expression of pro-osteoclastogenic genes in marrow and skeletal tissue

DOE PAGES

Alwood, Joshua S.; Shahnazari, Mohammad; Chicana, Betsabel; ...

2015-03-03

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically active, cancellous bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16 week), male C57BL/6J mice were exposed to either 2 Gy gamma rays ( 137Cs, 0.8 Gy/min) or heavy ions ( 56Fe, 600MeV, 0.50–1.1 Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is ≥10 Gy) ormore » accumulates over long-duration interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4 h—7 days later. Gamma irradiation caused a prompt (2.6-fold within 4 h) and persistent (peaking at 4.1-fold within 1 day) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappa-B ligand ( Rankl), within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3 days of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (eg, monocyte chemotactic protein-1 increased by 11.9-fold, and tumor necrosis factor-alpha increased by 1.7-fold over controls). The ratio, Rankl/ Opg, in marrow increased by 1.8-fold, a net pro-resorption balance. In the marrow, expression of the antioxidant transcription factor, Nfe2l2, strongly correlated with expression levels of Nfatc1, Csf1, Tnf, and Rankl. Radiation exposure increased a serum marker of bone resorption (tartrate-resistant acid phosphatase) and led to cancellous bone loss (16% decrement after 1 week). Finally, we conclude that total body irradiation (gamma or heavy-ion) caused temporal elevations in the concentrations of specific genes expressed within marrow and mineralized tissue related to bone resorption, including select cytokines that lead to osteoclastogenesis and elevated resorption; this is likely to account for rapid and progressive deterioration of cancellous microarchitecture following exposure to ionizing radiation.« less

Ionizing radiation stimulates expression of pro-osteoclastogenic genes in marrow and skeletal tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alwood, Joshua S.; Shahnazari, Mohammad; Chicana, Betsabel

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically active, cancellous bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16 week), male C57BL/6J mice were exposed to either 2 Gy gamma rays ( 137Cs, 0.8 Gy/min) or heavy ions ( 56Fe, 600MeV, 0.50–1.1 Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is ≥10 Gy) ormore » accumulates over long-duration interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4 h—7 days later. Gamma irradiation caused a prompt (2.6-fold within 4 h) and persistent (peaking at 4.1-fold within 1 day) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappa-B ligand ( Rankl), within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3 days of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (eg, monocyte chemotactic protein-1 increased by 11.9-fold, and tumor necrosis factor-alpha increased by 1.7-fold over controls). The ratio, Rankl/ Opg, in marrow increased by 1.8-fold, a net pro-resorption balance. In the marrow, expression of the antioxidant transcription factor, Nfe2l2, strongly correlated with expression levels of Nfatc1, Csf1, Tnf, and Rankl. Radiation exposure increased a serum marker of bone resorption (tartrate-resistant acid phosphatase) and led to cancellous bone loss (16% decrement after 1 week). Finally, we conclude that total body irradiation (gamma or heavy-ion) caused temporal elevations in the concentrations of specific genes expressed within marrow and mineralized tissue related to bone resorption, including select cytokines that lead to osteoclastogenesis and elevated resorption; this is likely to account for rapid and progressive deterioration of cancellous microarchitecture following exposure to ionizing radiation.« less

Syngeneic graft-versus-host disease: a report of two cases and literature review.

PubMed

Latif, T; Pohlman, B; Kalaycio, M; Sobecks, R; Hsi, E D; Andresen, S; Bolwell, B J

2003-09-01

Rappeport et al first reported the clinical syndrome of graft-versus-host disease (GVHD) in syngeneic bone marrow transplant patients. Recently, there have been more reports of a GVHD-like syndrome in syngeneic bone marrow transplant patients (SGVHD) that may result in significant clinical morbidity. A total of 17 cases of SGVHD in syngeneic bone marrow transplant patients have been reported to date in the medical literature. The current report reviews these cases and presents two additional cases of severe SGVHD that have occurred at our institution.

Hemopoietic progenitor cell function after HLA-identical sibling bone marrow transplantation: influence of chronic graft-versus-host disease.

PubMed

Atkinson, K; Norrie, S; Chan, P; Zehnwirth, B; Downs, K; Biggs, J

1986-05-01

We examined hemopoietic reconstitution during the first 12 months post-transplant in 31 patients given high-dose cyclophosphamide, total body irradiation and an HLA-identical sibling marrow transplant for hematological malignancy. Unexpectedly, we found marrow CFU-gm and marrow CFU-e cells to be denser than normal throughout the first year post-transplant. While functionally adequate neutrophil and platelet counts were achieved in the first six weeks post-transplant, there were defects in hemopoietic progenitor cell function during the first year post-transplant. Although we could detect no influence from acute graft-versus-host disease (GVHD), chronic GVHD adversely affected the growth of both myeloid and erythroid blood progenitor cells.

Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship

PubMed Central

Chen, J.; Gantz, M.; Punyanitya, M.; Heymsfield, S. B.; Gallagher, D.; Albu, J.; Engelson, E.; Kotler, D.; Pi-Sunyer, X.; Shapses, S.

2012-01-01

Summary The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. Introduction It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. Methods Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18–88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. Results A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r=−0.533, −0.576, respectively; P<0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premeno-pausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. Conclusions An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations. PMID:22173789

Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship.

PubMed

Shen, W; Chen, J; Gantz, M; Punyanitya, M; Heymsfield, S B; Gallagher, D; Albu, J; Engelson, E; Kotler, D; Pi-Sunyer, X; Shapses, S

2012-09-01

The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18-88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r = -0.533, -0.576, respectively; P < 0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premenopausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations.

Expansion of Endothelial Progenitor Cells in High Density Dot Culture of Rat Bone Marrow Cells

PubMed Central

Wang, Ling; Kretlow, James D.; Zhou, Guangdong; Cao, Yilin; Liu, Wei; Zhang, Wen Jie

2014-01-01

In vitro expansion of endothelial progenitor cells (EPCs) remains a challenge in stem cell research and its application. We hypothesize that high density culture is able to expand EPCs from bone marrow by mimicking cell-cell interactions of the bone marrow niche. To test the hypothesis, rat bone marrow cells were either cultured in high density (2×105 cells/cm2) by seeding total 9×105 cells into six high density dots or cultured in regular density (1.6×104 cells/cm2) with the same total number of cells. Flow cytometric analyses of the cells cultured for 15 days showed that high density cells exhibited smaller cell size and higher levels of marker expression related to EPCs when compared to regular density cultured cells. Functionally, these cells exhibited strong angiogenic potentials with better tubal formation in vitro and potent rescue of mouse ischemic limbs in vivo with their integration into neo-capillary structure. Global gene chip and ELISA analyses revealed up-regulated gene expression of adhesion molecules and enhanced protein release of pro-angiogenic growth factors in high density cultured cells. In summary, high density cell culture promotes expansion of bone marrow contained EPCs that are able to enhance tissue angiogenesis via paracrine growth factors and direct differentiation into endothelial cells. PMID:25254487

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia.

PubMed

Iwaniec, Urszula T; Turner, Russell T

2013-03-01

A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kit(W/W-v)) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to the development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kit(W/W-v) mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kit(W/W-v) mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kit(W/W-v) mice. However, ovx in WT and kit(W/W-v) mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Development and characterization of a lung-protective method of bone marrow transplantation in the mouse.

PubMed

Janssen, William J; Muldrow, Alaina; Kearns, Mark T; Barthel, Lea; Henson, Peter M

2010-05-31

Allogeneic bone marrow transplantation is a common method used to study the contribution of myeloid and lymphoid cell populations in murine models of disease. The method requires lethal doses of radiation to ablate the bone marrow. Unintended consequences of radiation include organ injury and inflammatory cell activation. The goal of our study was to determine the degree to which bone marrow transplantation alters lungs and to develop a system to protect the lungs during radiation. C57BL/6 mice were subjected to total body irradiation with 900cGy and then transplanted with bone marrow from green fluorescent protein (GFP) expressing mice. Resultant chimeras exhibited a significant decline in alveolar macrophage numbers within 72h, modest influx of neutrophils in the lungs at 14days, and repopulation of the lungs by alveolar macrophages of bone marrow origin by 28days. Neutrophil influx and alveolar macrophage turnover were prevented when 1cm thick lead shields were used to protect the lungs during radiation, such that 8weeks after transplantation less than 30% of alveolar macrophages were of donor origin. Lung-shielded mice achieved a high level of bone marrow engraftment with greater than 95% of circulating leukocytes expressing GFP. In addition, their response to intratracheal lipopolysaccharide was similar to non-transplanted mice. We describe a model whereby lead shields protect resident cell populations in the lungs from radiation during bone marrow transplantation but permit full bone marrow engraftment. This system may be applicable to other organ systems in which protection from radiation during bone marrow transplantation is desired.

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting.

PubMed

Arroz, Maria; Came, Neil; Lin, Pei; Chen, Weina; Yuan, Constance; Lagoo, Anand; Monreal, Mariela; de Tute, Ruth; Vergilio, Jo-Anne; Rawstron, Andy C; Paiva, Bruno

2016-01-01

Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing. A group of 11 flow cytometrists currently performing FC testing in MM using different instrumentation, panel designs (≥ 6-color) and analysis software compared the procedures between their respective laboratories and reviewed the literature to propose a consensus guideline on flow-MRD analysis and reporting in MM. Consensus guidelines support i) the use of minimum of five initial gating parameters (CD38, CD138, CD45, forward, and sideward light scatter) within the same aliquot for accurate identification of the total plasma cell compartment; ii) the analysis of potentially aberrant phenotypic markers and to report the antigen expression pattern on neoplastic plasma cells as being reduced, normal or increased, when compared to a normal reference plasma cell immunophenotype (obtained using the same instrument and parameters); and iii) the percentage of total bone marrow plasma cells plus the percentages of both normal and neoplastic plasma cells within the total bone marrow plasma cell compartment, and over total bone marrow cells. Consensus guidelines on minimal current and future MRD analyses should target a lower limit of detection of 0.001%, and ideally a limit of quantification of 0.001%, which requires at least 3 × 10(6) and 5 × 10(6) bone marrow cells to be measured, respectively. © 2015 International Clinical Cytometry Society.

Three-Dimensional Dose Calculation for Total Body Irradiation

NASA Astrophysics Data System (ADS)

Ito, Akira

Bone Marrow Transplant (BMT) therapy has been a big success in the treatment of leukemia and other haematopoietic diseases 1 . Prior to BMT, total body irradiation (TBI) is given to the patient for the purpose of (1) killing leukemia cells in bone marrow, as well as in the whole body, and (2) producing immuno-suppressive status in the patient so that the donor's marrow cells will be transplanted without rejection. TBI employs a very large field photon beam to irradiate the whole body of the patient. A uniform dose distribution over the entire body is the treatment goal. To prevent the occurrence of a serious side effect (interstitial pneumonia), the lung dose should not exceed a certain level. This novel technique poses various new radiological physics problems. The accurate assessment of dose and dose distribution in the patient is essential. Physical and dosimetric problems associated with TBI are reviewed elsewhere 2,3 .

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokines

PubMed Central

Brusnahan, S.K.; McGuire, T.R.; Jackson, J.D.; Lane, J.T.; Garvin, K.L.; O’Kane, B.J.; Berger, A.M.; Tuljapurkar, S.R.; Kessinger, M.A.; Sharp, J.G.

2010-01-01

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N = 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2 mm fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. PMID:21035480

The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.

1990-12-01

To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease inmore » bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation.« less

Association between Activated Partial Thromboplastin Time and the Amount of Infused Heparin at Bone Marrow Transplantation.

PubMed

Kusuda, Machiko; Kimura, Shun-Ichi; Misaki, Yukiko; Yoshimura, Kazuki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Ugai, Tomotaka; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Tanihara, Aki; Kanda, Yoshinobu

2018-03-27

The actual heparin concentration of harvested allogeneic bone marrow varies among harvest centers. We monitor the activated partial thromboplastin time (APTT) of the patient during bone marrow infusion and administer prophylactic protamine according to the APTT. We retrospectively reviewed the charts of consecutive patients who underwent bone marrow transplantation without bone marrow processing at our center between April 2007 and March 2016 (n = 94). APTT was monitored during marrow transfusion in 52 patients. We analyzed the relationship between the APTT ratio and several parameters related to heparin administration. As a result, the weight-based heparin administration rate (U/kg/hour) seemed to be more closely related to the APTT ratio (r = .38, P = .005) than to the total amount of heparin. There was no significant correlation between the APTT ratio and renal or liver function. Bleeding complications during and early after infusion were seen in 3 of 52 patients, and included intracranial, nasal, and punctured-skin bleeding. The APTT ratio during transfusion was over 5.88 in the former 2 patients and 2.14 in the latter. All of these patients recovered without sequelae. In conclusion, slow bone marrow infusion is recommended to decrease the weight-based heparin administration rate when the heparin concentration per patient body weight is high. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis

PubMed Central

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L.; Wang, Yanlin

2014-01-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. Since chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly fewer bone marrow-derived fibroblasts accumulated in the kidney of CXCR6 knockout mice in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type mice. CXCR6 deficiency inhibited total collagen deposition and suppressed expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, wild type mice engrafted with CXCR6−/− bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with wild-type mice engrafted with CXCR6+/+ bone marrow cells. Transplant of wild type bone marrow into CXCR6−/− recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may play important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis. PMID:24646857

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis.

PubMed

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L; Wang, Yanlin

2014-08-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, and they proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. As chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly, the kidney of CXCR6 knockout mice accumulated fewer bone marrow-derived fibroblasts in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type (WT) mice. CXCR6 deficiency inhibited total collagen deposition and suppressed the expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, WT mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with WT mice engrafted with CXCR6(+/+) bone marrow cells. Transplant of WT bone marrow into CXCR6(-/-) recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may have important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis.

Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2−/−) Mice

PubMed Central

Berhane, Hebist; Epperly, Michael W.; Goff, Julie; Kalash, Ronny; Cao, Shaonan; Franicola, Darcy; Zhang, Xichen; Shields, Donna; Houghton, Frank; Wang, Hong; Wipf, Peter; Parmar, Kalindi; Greenberger, Joel S.

2014-01-01

FancD2 plays a central role in the human Fanconi anemia DNA damage response (DDR) pathway. Fancd2−/− mice exhibit many features of human Fanconi anemia including cellular DNA repair defects. Whether the DNA repair defect in Fancd2−/− mice results in radiologic changes in all cell lineages is unknown. We measured stress of hematopoiesis in long-term marrow cultures and radiosensitivity in clonogenic survival curves, as well as comet tail intensity, total antioxidant stores and radiation-induced gene expression in hematopoietic progenitor compared to bone marrow stromal cell lines. We further evaluated radioprotection by a mitochondrial-targeted antioxidant GS-nitroxide, JP4-039. Hematopoiesis longevity in Fancd2−/− mouse long-term marrow cultures was diminished and bone marrow stromal cell lines were radiosensitive compared to Fancd2+/+ stromal cells (Fancd2−/− D0 = 1.4 ± 0.1 Gy, ñ = 5.0 ± 0.6 vs. Fancd2+/+ D0 = 1.6 ± 0.1 Gy, ñ = 6.7 ± 1.6), P = 0.0124 for D0 and P = 0.0023 for ñ, respectively). In contrast, Fancd2−/− IL-3-dependent hematopoietic progenitor cells were radioresistant (D0 = 1.71 ± 0.04 Gy and ñ = 5.07 ± 0.52) compared to Fancd2+/+ (D0 = 1.39 ± 0.09 Gy and ñ = 2.31 ± 0.85, P = 0.001 for D0). CFU-GM from freshly explanted Fancd2−/− marrow was also radioresistant. Consistent with radiosensitivity, irradiated Fancd2−/− stromal cells had higher DNA damage by comet tail intensity assay compared to Fancd2+/+ cells (P < 0.0001), slower DNA damage recovery, lower baseline total antioxidant capacity, enhanced radiation-induced depletion of antioxidants, and increased CDKN1A-p21 gene transcripts and protein. Consistent with radioresistance, Fancd2−/− IL-3-dependent hematopoietic cells had higher baseline and post irradiation total antioxidant capacity. While, there was no detectable alteration of radiation-induced cell cycle arrest with Fancd2−/− stromal cells, hematopoietic progenitor cells showed reduced G2/M cell cycle arrest. The absence of the mouse Fancd2 gene product confers radiosensitivity to bone marrow stromal but not hematopoietic progenitor cells. PMID:24397476

Erythroleukemia shares biological features and outcome with myelodysplastic syndromes with excess blasts: a rationale for its inclusion into future classifications of myelodysplastic syndromes.

PubMed

Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

2016-12-01

Erythroleukemia was considered an acute myeloid leukemia in the 2008 World Health Organization (WHO) classification and is defined by the presence of ≥50% bone marrow erythroblasts, having <20% bone marrow blasts from total nucleated cells but ≥20% bone marrow myeloblasts from nonerythroid cells. Erythroleukemia shares clinicopathologic features with myelodysplastic syndromes, especially with erythroid-predominant myelodysplastic syndromes (≥50% bone marrow erythroblasts). The upcoming WHO revision proposes to eliminate the nonerythroid blast cell count rule and to move erythroleukemia patients into the appropriate myelodysplastic syndrome category on the basis of the absolute blast cell count. We conducted a retrospective study of patients with de novo erythroleukemia and compared their clinico-biological features and outcome with those of de novo myelodysplastic syndromes, focusing on erythroid-predominant myelodysplastic syndromes. Median overall survival of 405 erythroid-predominant myelodysplastic syndromes without excess blasts was significantly longer than that observed in 57 erythroid-predominant refractory anemias with excess blasts-1 and in 59 erythroleukemias, but no significant difference was observed between erythroid-predominant refractory anemias with excess blasts-1 and erythroleukemias. In this subset of patients with ≥50% bone marrow erythroblasts and excess blasts, the presence of a high-risk karyotype defined by the International Prognostic Scoring System or by the Revised International Prognostic Scoring System was the main prognostic factor. In the same way, the survival of 459 refractory anemias with excess blasts-2, independently of having ≥20% bone marrow blasts from nonerythroid cells or not, was almost identical to the observed in 59 erythroleukemias. Interestingly, 11 low-blast count erythroleukemias with 5 to <10% bone marrow blasts from total nucleated cells showed similar survival than the rest of erythroleukemias. Our data suggest that de novo erythroleukemia is in the spectrum of myelodysplastic syndromes with excess blasts and support its inclusion into future classifications of myelodysplastic syndromes.

Prostaglandin E2 Increased Rat Cortical Bone Mass When Administered Immediately Following Ovariectomy

NASA Technical Reports Server (NTRS)

Ke, Hua Zhu; Jee, Webster S.S.; Zeng, Qing Qiang; Li, Mei; Lin, Bai Yun

1993-01-01

To investigate the effects of ovariectomy and the simultaneous administration of prostaglandin E2 (PGE2) on rat tibial shaft cortical bone histomorphometry, thirty-five 3 month-old female Sprague-Dawley rats were either ovariectomized (OVX), or sham ovariectomy (sham-OVX). The OVX rats were divided into three groups and treated with 0, 1 and 6 mg PGE2/kg/day for 90 days. The double fluorescent labeled undecalcified tibial shaft cross sections (proximal to the tibiofibular junction) of all the subjects were used for histomorphometry analysis. No differences in cross-sectional area and cortical bone area were found between sham-OVX and OVX controls, but OVX increased marrow area, intracortical porosity area and endocortical eroded perimeter. Periosteal and endocortical bone formation rates decreased with aging yet OVX prevented these changes. These OVX-induced increases in marrow area and endocortical eroded perimeter were prevented by 1 mg PGE2/kg/day treatment and added bone to periosteal and endocortical surfaces and to the marrow cavity. At the 6 mg/kg/day dose level, PGE2-treated OVX rats increased total tissue area, cortical bone area, marrow trabmular bone area, minimal cortical width and intracortical porosity area, and decreased marrow area compared to basal, sham-OVX and OVX controls. In addition, periosteal bone formation was elevated in the 6 mg PGE2/kg/day-treated OVX rats compared to OVX controls. Endocortical eroded perimeter increased from basal and sham-OVX control levels, but decreased from OVX control levels in the 6 mg PGE2/kg/day-treated OVX rats. Our study confirmed that ovariectomy does not cause osteopenia in tibial shaft cortical bone in rats, but it does stimulate endocortical bone resorption and enlarges marrow area. The new findings from the present study demonstrate that PGE2 prevents the OVX-induced increases in endocortical bone resorption and marrow area and adds additional bone to periosteal and endocortical surfaces and to marrow cavity to increase total bone mass in the tibial shaft of OVX rats when given immediately following ovafiectomy.

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Storb, R.; Raff, R.F.; Graham, T.

1993-03-20

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionatedmore » total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.« less

Reduced adiposity in ob/ob mice following total body irradiation and bone marrow transplantation.

PubMed

Ablamunits, Vitaly; Weisberg, Stuart P; Lemieux, Jacob E; Combs, Terry P; Klebanov, Simon

2007-06-01

The objective of this study was to assess long-term metabolic consequences of total body irradiation (TBI) and bone marrow transplantation. Severe obesity develops due to both hypertrophy and hyperplasia of adipocytes. We hypothesized that TBI would arrest adipose tissue growth and would affect insulin resistance (IR). We exposed 2-month-old female ob/ob mice to 8 Grays of TBI followed by bone marrow transplantation and tested the animals for body weight (BW) gain, body composition, blood glucose, and insulin sensitivity. Two months after TBI, irradiated mice stopped gaining BW, whereas non-treated mice continued to grow. At the age of 9.5 months, body mass of irradiated mice was 60.6 +/- 1.4 grams, which was only 61% of that in non-treated ob/ob controls (99.4 +/- 1.6 grams). Body composition measurements by DXA showed that decreased BW was primarily due to an impaired fat accumulation. This could not result from the production of leptin by bone marrow-derived adipocyte progenitors because inhibition of the obese phenotype was identical in recipients of both B6 and ob/ob bone marrow. Inability of the irradiated mice to accumulate fat was associated with hepatomegaly, lower levels of monocyte chemoattractant protein-1 expression in adipose tissue, and increased IR. Our data argue in favor of the hypothesis that inability of adipose tissue to expand may increase IR. This mouse model may be valuable for studies of late-onset radiation-induced IR in humans.

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines.

PubMed

Brusnahan, S K; McGuire, T R; Jackson, J D; Lane, J T; Garvin, K L; O'Kane, B J; Berger, A M; Tuljapurkar, S R; Kessinger, M A; Sharp, J G

2010-01-01

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Prevalence and Implications of Bone Marrow Involvement in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

PubMed Central

Choi, Sang Il; Kook, Myeong-Cherl; Hwang, Sanghyun; Kim, Young-Il; Lee, Jong Yeul; Kim, Chan Gyoo; Choi, Il Ju; Lee, Hyewon; Eom, Hyeon Seok

2018-01-01

Background/Aims Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. PMID:29409307

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 safely used in-treatment.

High stress shallow moonquakes - Evidence for an initially totally molten moon

NASA Technical Reports Server (NTRS)

Binder, A. B.; Oberst, J.

1985-01-01

Thermoelastic stress calculations show that if the moon was initially molten only in the outer few hundred kilometers, as in the magma ocean model of the moon, the highlands crust should be aseismic. In contrast, if the moon was initially totally molten, high stress (1 to more than about 3 kbar), shallow (0 to about 6 km deep), compressional moonquakes should be occurring in the highlands crust. Calculations of the minimum stress drops made for the 28 observed shallow moonquakes suggest that 3 of them probably have stress drops in the kbar range. Thus, these very limited seismic data are consistent with the model that the moon was initially totally molten.

Bacteriological findings in patients with bone marrow transplantation (Karl Marx University Leipzig, 1985-1987).

PubMed

Wonitzki, C; Hoffmann, F A

1989-01-01

The results of the bacteriological surveillance cultures for 26 patients with bone marrow transplantation (Karl Marx University Leipzig, G.D.R., 1985-1987) are presented. 5.9% of all surveillance cultures contained facultatively pathogenic germs (with Pseudomonas aeruginosa as the most frequent representative, which was the reason of a sepsis in two patients). Coagulasenegative Staphylococci and other germs with an obscure pathogenicity were isolated upon a large scale, especially from the mucous membrane regions. There are hints, that above all special strains of coagulasenegative Staphylococci "colonize" the patient's body (also for longer periods) and turn into the blood too. During the total decontamination intestinal anaerobic flora is absent. After closing of total decontamination Clostridium perfringens is the first detectable anaerobic species. During the selective decontamination systemic applications of antibiotics are able to obliterate anaerobic findings for certain periods. Recommendations for an effective arrangement of the surveillance cultures of bone marrow transplantation patients are given.

Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants.

PubMed

Vuola, J; Göransson, H; Böhling, T; Asko-Seljavaara, S

1996-09-01

In this experimental study, blocks of natural coral (calcium carbonate) and its structurally similar derivate in the form of hydroxyapatite (calcium phosphate) were implanted in rat latissimus dorsi muscle with autogenous bone marrow to compare their bone-forming capability. A block without marrow placed in the opposite latissimus muscle served as a control. The animals were killed at 3, 6 and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections were analysed histologically and histomorphometrically. Bone was found only in implants containing bone marrow. Bone formation was significantly (p < 0.05) higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%) and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks all the coral implants had lost their original structure, and the cross-sectional area of the block had diminished to 40% of the original area.

Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion.

PubMed

Baxter, Melissa A; Wynn, Robert F; Jowitt, Simon N; Wraith, J Ed; Fairbairn, Leslie J; Bellantuono, Ilaria

2004-01-01

Human marrow stromal cells (MSCs) can be isolated from bone marrow and differentiate into multiple tissues in vitro and in vivo. These properties make them promising tools in cell and gene therapy. The lack of a specific MSC marker and the low frequency of MSCs in bone marrow necessitate their isolation by in vitro expansion prior to clinical use. This may severely reduce MSC proliferative capacity to the point that the residual proliferative potential is insufficient to maintain long-term tissue regeneration upon reinfusion. In this study we determined the effect of in vitro expansion on the replicative capacity of MSCs by correlating their rate of telomere loss during in vitro expansion with their behavior in vivo. We report that even protocols that involve minimal expansion induce a rapid aging of MSCs, with losses equivalent to about half their total replicative lifespan.

Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro.

PubMed

Redondo, Juliana; Sarkar, Pamela; Kemp, Kevin; Virgo, Paul F; Pawade, Joya; Norton, Aimie; Emery, David C; Guttridge, Martin G; Marks, David I; Wilkins, Alastair; Scolding, Neil J; Rice, Claire M

2017-05-01

Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this study was provided by the Medical Research Council, UK (grant no. MR/K004166/1). The ACTiMuS study is sup-ported by the Silverman Family Foundation, Multiple Sclerosis Trust, Rosetree’s Trust, Catholic Bishops of England and Wales and Friends of Frenchay and SIAMMS-II by the Sir Halley Stewart Trust. C.M.R., P.S., and K.K. received support from the Burden Neurological Institute.

[Autologous bone marrow transplantation in intestinal carcinoma].

PubMed

Sebesta, C; Tiefengraber, E; Kier, P; Ruckser, R; Habertheuer, K H; Schmid, A; Hinterberger, W

1995-01-01

Although adjuvant chemotherapy has made some progress in the treatment of colorectal cancer, chemotherapy of metastatic disease remains disappointing. Autologous bone marrow or stem cell transplantation following supralethal chemotherapy is presently not of major significance in tumors of the intestine. The registry of the EBMT (European Cooperative Group for Blood and Marrow Transplantation) contains at March 1993 a total of 2085 cases of autotransplants for solid tumors, of which only 19 were performed for disseminated gastrointestinal cancer (15 gastric, 4 colon). It remains to be shown, whether the presently poor results can be improved upon inclusion of lymphokine-activated killer cells (LAK-cells) by use of cytokine combinations or by the use of tumor infiltrating lymphocytes (TIL) post transplantation.

Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients.

PubMed

Hernigou, Philippe; Dubory, Arnaud; Homma, Yasuhiro; Guissou, Isaac; Flouzat Lachaniette, Charles Henri; Chevallier, Nathalie; Rouard, Hélène

2018-05-09

Symptomatic osteonecrosis related to corticosteroids has a high risk of progression to collapse in absence of treatment. The purposes of this study were to evaluate the results of autologous bone marrow grafting of the symptomatic hip in adult patients with osteonecrosis and to compare the results with core decompression alone in the contralateral symptomatic hip. A total of 125 consecutive patients (78 males and 47 females) with bilateral osteonecrosis (ON) and who had both hips symptomatic and at the same stage on each side (stage I or II) were included in this study from 1988 to 1998. The volume of osteonecrosis was measured with MRI in both hips; the smaller size ON was treated with core decompression, and the contralateral hip with the larger ON was treated with percutaneous mesenchymal cell (MSC) injection obtained from bone marrow concentration. The average total number of MSCs (counted as number of colony forming units-fibroblast) injected in each hip was 90,000 ± 25,000 cells (range 45,000 to 180,000 cells). At the most recent FU (average 25 years after the first surgery, range 20 to 30 years), among the 250 hips included in the study, 35 hips (28%) had collapsed at the most recent follow-up after bone marrow grafting, and 90 (72%) after core decompression (CD). Ninety-five hips (76%) in the CD group underwent total hip replacement and 30 hips (24%) in the bone marrow graft group (p < 0.0001). Hips undergoing only CD were approximately three times more likely to undergo a primary THA (odds ratio: 10.0278; 95% CI: 5.6117 to 17.9190; p < 0.0001) as compared with hips undergoing an initial bone marrow grafting. For the 90 hips treated with bone marrow injection and without collapse, the mean volume of repair evaluated by MRI at the most recent follow-up was 16.4 cm 3 (range 12 to 21 cm 3 ) corresponding to a decrease of the pre-operative average volume from 22.4 cm 3 (range 35-15 cm 3 ) to 6 cm 3 (range 12-0 cm 3 ); as percentage of the volume of the femoral head, the decrease moved from 44.8 to 12%. Core decompression with bone marrow injection improved the outcome of the disease as compared with core decompression alone in the same patient.

Functionally deficient mesenchymal stem cells reside in the bone marrow niche with M2-macrophages and amyloid-β protein adjacent to loose total joint implants.

PubMed

Margulies, Bryan S; DeBoyace, Sean D; Parsons, Adrienne M; Policastro, Connor G; Ee, Jessica S S; Damron, Timothy S

2015-05-01

We sought to demonstrate whether there is a difference in the local mesenchymal stem cells (MSC) niche obtained from patients undergoing their first total joint replacement surgery versus those patients undergoing a revision surgery for an failing total joint implant. Bone marrow aspirates collected from patients undergoing revision total joint arthroplasty were observed to be less clonal and the expression of PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, and nucleostemin were decreased. Revision MSC were also less able to commit to an osteoblast-lineage or an adipocyte-lineage. Further, in revision MSC, OPG, and IL6 expression were increased. Monocytes, derived from revision whole marrow aspirates, were less capable of differentiating into osteoclasts, the cells implicated in the pathologic degradation of bone. Osteoclasts were also not observed in tissue samples collected adjacent to the implants of revision patients; however, the alternatatively activated M2-macrophage phenotype was observed in parallel with pathologic accumulations of amyloid-β, τ-protien and 3-nitrotyrosine. Despite the limited numbers of patients examined, our data suggest that nucleostemin may be a useful functional marker for MSC while the observation of M2-macrophage infiltration around the implant lays the foundation for future investigation into a novel mechanism that we propose is associated with loose total joint implants. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning

PubMed Central

Hogan, William; Kuhr, Christian S.; Diaconescu, Razvan; Harkey, Michael A.; Georges, George E.; Sale, George E.; Zellmer, Eustacia; Baran, Szczepan; Jochum, Christoph; Stone, Brad; Storb, Rainer

2007-01-01

Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial “trichimerism,” which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors. PMID:17369487

External bone marrow cytological examination quality assurance (EQAhem)--summary after 6 years in Poland.

PubMed

Lewandowski, Krzysztof; Kurpierz, Katarzyna; Sledzinska, Anna

2015-10-01

Bone marrow macroscopic examination remains one of the most difficult and subjective laboratory assessments in hematology. Only a few external quality assurance programs in the field are present worldwide. We have developed an external quality assurance program EQAhem that allows assessment of the whole process of bone marrow examination. The program participants assess blood and bone marrow smears from the patient, identify selected cells from photographs provided to them, and interpret the microscopic results. In this article, the results of the EQAhem program in Poland from 6 years are summarized. During this time, 62 labs were assessed in total, and positive results were achieved by 89.25 % labs, taking into account all tests. Correct responses with respect to the percentage of cell count were provided by ca. 77.5 % labs. Slightly worse results were obtained when megakaryocyte count and cell identification from photographs were tested. The worst results were obtained in case of dysplasia assessment and clinical interpretation of microscopic examination (54.1 and 58.6 % correct responses, respectively). EQAhem delivers precise information about the quality of bone marrow examinations performed in Poland and has a substantial educational value. We believe that after 6 years, EQAhem has significantly improved the quality of bone marrow microscopic examinations performed in Poland.

In vitro osteoblastic differentiation of human bone marrow cells in the presence of metal ions.

PubMed

Morais, S; Dias, N; Sousa, J P; Fernandes, M H; Carvalho, G S

1999-02-01

For periods up to 21 days human bone marrow was cultured in control conditions that favor the proliferation and differentiation of osteoblastic cells. The effect of AISI 316L corrosion products and the corresponding major separate metal ions (Fe, Cr, and Ni) were studied in three different phases of the culture period in order to investigate the effects of metal ions in cell populations representative of osteoblastic cells in different stages of differentiation. Toxicity consequences of the presence of metal ions in bone marrow cultures were evaluated by biochemical parameters (enzymatic reduction of MTT, alkaline phosphatase activity, and total protein content), histochemical assays (identification of ALP-positive cells and Ca and phosphates deposits), and observation of the cultures by light and scanning electron microscopy. Culture media were analyzed for total and ionized Ca and P and also for metal ions (Fe, Cr, and Ni). The presence of AISI 316L corrosion products and Ni salt in bone marrow cultures during the first and second weeks of culture significantly disturbs the normal behavior of these cultures, interfering in the lag phase and exponential phase of cell growth and ALP expression. However, the presence of these species during the third week of culture, when expression of osteoblastic functions occurs (mineralization process), did not result in any detectable effect. Fe salt also disturbs the behavior of bone marrow cell cultures when present during the lag phase and proliferation phase, and a somewhat compromised response between the normal pattern (control cultures) and intense inhibition (AISI 316L corrosion products and Ni salt-added cultures) was observed. Fe did not affect the progression of the mineralization phase. Osteogenic cultures exposed to Cr salt (Cr3+) presented a pattern similar to the controls, indicating that this element does not interfere, in the concentration studied, in the osteoblastic differentiation of bone marrow cells. Quantification of metal ions in the culture media showed that Cr (originated from AISI 316L corrosion products but from not Cr3+ salt) and Ni (originated from AISI 316L corrosion products and Ni salt) appear to be retained by the bone marrow cultures. Copyright 1999 John Wiley & Sons, Inc.

Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells.

PubMed

Zhang, Qiu Hua; Wu, Chun Fu; Duan, Lian; Yang, Jing Yu

2008-01-01

Cyclophosphamide (CP), commonly used anti-cancer, induces oxidative stress and is cytotoxic to normal cells. It is very important to choice the protective agent combined CP to reduce the side effects in cancer treatment. Ginsenosides are biological active constituents of Panax ginseng C.A. Meyer that acts as the tonic agent for the cancer patients to reduce the side effects in the clinic application. Because CP is a pro-oxidant agent and induces oxidative stress by the generation of free radicals to decrease the activities of anti-oxidant enzymes, the protective effects of the total saponins from stem and leaf of P. ginseng C.A. Meyer (TSPG) act as an anti-oxidant agent against the decreased anti-oxidant enzymes, the genotoxicity and apoptosis induced by CP was carried out. The alkaline single cell gel electrophoresis was employed to detect DNA damage; flow cytometry assay and AO/EB staining assay were employed to measure cell apoptosis; the enzymatic anti-oxidants (T-SOD, CAT and GPx) and non-enzymatic anti-oxidant (GSH) were measured by the various colorimetric methods. CP induced the significant DNA damage in mouse peripheral lymphocytes in time- and dose-dependent manners, inhibited the activities of T-SOD, GPx and CAT, and decreased the contents of GSH in mouse blood, triggered bone marrow cell apoptosis at 6 and 12h. TSPG significantly reduced CP-induced DNA damages in bone marrow cells and peripheral lymphocyte cells, antagonized CP-induced reduction of T-SOD, GPx, CAT activities and the GSH contents, decreased the bone marrow cell apoptosis induced by CP. TSPG, significantly reduced the genotoxicity of CP in bone marrow cells and peripheral lymphocyte cells, and decreased the apoptotic cell number induced by CP in bone marrow cells. The effects of TSPG on T-SOD, GPx, CAT activities and GSH contents might partially contribute to its protective effects on CP-induced cell toxicities.

Improved bone marrow stromal cell adhesion on micropatterned titanium surfaces.

PubMed

Iskandar, Maria E; Cipriano, Aaron F; Lock, Jaclyn; Gott, Shannon C; Rao, Masaru P; Liu, Huinan

2012-01-01

Implant longevity is desired for all bone replacements and fixatives. Titanium (Ti) implants fail due to lack of juxtaposed bone formation, resulting in implant loosening. Implant surface modifications have shown to affect the interactions between the implant and bone. In clinical applications, it is crucial to improve osseointegration and implant fixation at the implant and bone interface. Moreover, bone marrow derived cells play a significant role for implant and tissue integration. Therefore, the objective of this study is to investigate how surface micropatterning on Ti influences its interactions with bone marrow derived cells containing mesenchymal and hematopoietic stem cells. Bone marrow derived mesenchymal stem cells (BMSC) have the capability of differentiating into osteoblasts that contribute to bone growth, and therefore implant/bone integration. Hematopoietic stem cell derivatives are precursor cells that contribute to inflammatory response. By using all three cells naturally contained within bone marrow, we mimic the physiological environment to which an implant is exposed. Primary rat bone marrow derived cells were seeded onto Ti with surfaces composed of arrays of grooves of equal width and spacing ranging from 0.5 to 50 µm, fabricated using a novel plasma-based dry etching technique. Results demonstrated enhanced total cell adhesion on smaller micrometer-scale Ti patterns compared with larger micrometer-scale Ti patterns, after 24-hr culture. Further studies are needed to determine bone marrow derived cell proliferation and osteogenic differentiation potential on micropatterned Ti, and eventually nanopatterned Ti.

CHARACTERIZATION OF FATTY ACID COMPOSITION IN BONE MARROW FLUID FROM POSTMENOPAUSAL WOMEN: MODIFICATION AFTER HIP FRACTURE

PubMed Central

Miranda, Melissa; Pino, Ana María; Fuenzalida, Karen; Rosen, Clifford J.; Seitz, Germán; Rodríguez, J. Pablo

2016-01-01

Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65 to 80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. PMID:27416518

[Sleep disorder of schizophrenia treated with shallow needling: a randomized controlled trial].

PubMed

Huang, Yanxi; Zheng, Ying

2015-09-01

To compare the clinical effective differences between shallow needling and medication for the sleep disorder of schizophrenia. Ninety-six patients with the sleep disorder of schizophrenia were randomly divided into a shallow needling group and a medication group, 48 cases in each one (one case dropping in the shallow needling group and two cases dropping in the medication group). The same dose paliperidone tablets were adopted in the two groups. In the shallow needling group, the main acupoints were Baihui (GV 20), Shangenxue (Extra) and Ezhongxian (MS 1), and the acupoints based on syndrome differentiation were selected. The shallow needling manipulation was used once a day, 5 times a week. In the medication group, 3 mg eszopiclone tablets were prescribed orally before sleep once every night. The patients were treated for 6 weeks in the two groups. Sleep condition was evaluated by Pittsburgh sleep quality index (PSQI) before and after treatment, and the clinical efficacy and the adverse reaction were assessed by positive and negative symptoms scale (PANSS) and treatment emergent symptom scale (TESS) before and after 2-week, 4-week and 6-week treatment. The clinical effects between the two groups were compared. After treatment in the two groups, both the total scores and the each factor score of the PSQI and the PANSS were apparently decreased (P<0. 05, P<0. 01). As for the PSQI scale, after treatment the daytime dysfunctional score of the shallow needling group was reduced more obviously than that of the medication group (P<0. 05), and the falling asleep time in the medication group was declined more markedly compared with that in the shallow needling group (P<0. 05). Regarding the PANSS, the improvement of the pathological factor in the shallow needling group was better than that in the medication group after treatment (P<0. 05), and the improvement of the positive factor in the medication group was superior to that in the shallow needling group after treatment (P<0. 05). The total scores and each factor score of the PSQI and the PANSS were not statistically different between the two groups after treatment (P>0. 05). At the end of the 6th week, the curative and effective rate was 63. 9% (30/47) and the total effective rate was 95. 8% (45/47) in the shallow needling group;the curative and effective rate was 58. 7% (27/46) and the total effective rate was 91. 3% (42/46) in the medication group. The difference of the effect was not statistically significant between the two groups (P>0. 05). The scores of TESS in the shallow needling group were lower than those in the medication group (P<0. 01, P<0. 05). The effect of shallow needling for assisting the sleeping disorder of schizophrenia is reliable and it is similar with the efficacy of eszopiclone. Also, the shallow needling can improve the daytime dysfunction and the pathological factor apparently without adverse reaction and pain. Its safety is obviously better than that of eszopiclone.

Unique Proteins Expressed by Blood Vessels in Skeletal Sites Colonized by Breast Cancer Cells

DTIC Science & Technology

2005-08-01

labeled acetylated LDL at an accelerated rate (3). After one week in culture BVECs and MVECs were harvested. Total RNA was extracted from both cell...bones where breast cancer cells tend to lodge, as compared to the vasculature of the central marrow cavity. We have found differences in RNA expression...by microarray analysis. The bone-derived vasculature expresses five RNA messages in greater abundance (2-fold or more) than the marrow-derived

The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Seon Young; Chung, Hee-Yong

2005-10-21

In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents inmore » bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.« less

Dietary Antioxidants Protect Hematopoietic Cells and Improve Animal Survival after Total-Body Irradiation

PubMed Central

Wambi, Chris; Sanzari, Jenine; Wan, X. Steven; Nuth, Manunya; Davis, James; Ko, Ying-Hui; Sayers, Carly M.; Baran, Matthew; Ware, Jeffrey H.; Kennedy, Ann R.

2009-01-01

The purpose of this study was to determine whether a dietary supplement consisting of L-selenomethionine, vitamin C, vitamin E succinate, α-lipoic acid and N-acetyl cysteine could improve the survival of mice after total-body irradiation. Antioxidants significantly increased the 30-day survival of mice after exposure to a potentially lethal dose of X rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 h after 1 Gy and 8 Gy. Antioxidants were effective in preventing peripheral lymphopenia only after low-dose irradiation. Antioxidant supplementation was also associated with increased bone marrow cell counts after irradiation. Supplementation with antioxidants was associated with increased Bcl2 and decreased Bax, caspase 9 and TGF-β1 mRNA expression in the bone marrow after irradiation. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow after sublethal or potentially lethal irradiation. Taken together, oral supplementation with antioxidants appears to be an effective approach for radioprotection of hematopoietic cells and improvement of animal survival, and modulation of apoptosis is implicated as a mechanism for the radioprotection of the hematopoietic system by antioxidants. PMID:18363433

Reciprocal Relation between Marrow Adiposity and the Amount of Bone in the Axial and Appendicular Skeleton of Young Adults

PubMed Central

Di Iorgi, Natascia; Rosol, Michael; Mittelman, Steven D.; Gilsanz, Vicente

2008-01-01

Background: Studies in the elderly suggest a reciprocal relation between increased marrow adiposity and bone loss, supporting basic research data indicating that osteoblasts and adipocytes share a common progenitor cell. However, whether this relation represents a preferential differentiation of stromal cells from osteoblasts to adipocytes or whether a passive accumulation of fat as bone is lost and marrow space increases with aging is unknown. To address this question and avoid the confounding effect of bone loss, we examined teenagers and young adults. Methods: Using computed tomography, we obtained measurements of bone density and cross-sectional area of the lumbar vertebral bodies and cortical bone area, cross-sectional area, marrow canal area, and fat density in the marrow of the femurs in 255 sexually mature subjects (126 females, 129 males; 15–24.9 yr of age). Additionally, values for total body fat were obtained with dual-energy x-ray absorptiometry. Results: Regardless of gender, reciprocal relations were found between fat density and measures of vertebral bone density and femoral cortical bone area (r = 0.19–0.39; all P values ≤ .03). In contrast, there was no relation between marrow canal area and cortical bone area in the femurs, neither between fat density and the cross-sectional dimensions of the bones. We also found no relation between anthropometric or dual-energy x-ray absorptiometry fat values and measures for marrow fat density. Conclusions: Our results indicate an inverse relation between bone marrow adiposity and the amount of bone in the axial and appendicular skeleton and support the notion of a common progenitor cell capable of mutually exclusive differentiation into the cell lineages responsible for bone and fat formation. PMID:18381577

Marrow Ablative and Immunosuppressive Effects of I-131-anti-CD45 Antibody in Congenic and H2-Mismatched Murine Transplant Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, D. C.; Martin, P J.; Nourigat, C.

1998-12-01

Targeted hematopoietic irradiation delivered by I-131-anti-CD45 antibody has been combined with conventional marrow transplant preparative regimens in an effort to decrease relapse. Before increasing the proportion of therapy delivered by radiolabeled antibody, the myeloablative and immunosuppressive effects of such low dose rate irradiation must be quantitated. We have examined the ability of I-131-anti-CD45 antibody to facilitate engraftment in Ly5-congenic and H2-mismatched murine marrow transplant models. Recipient B6-Ly5-a mice were treated with 30F11 antibody labeled with 0.1 to 1.5 mCi I-131 and/or total body irradiation (TBI), followed by T-cell-depleted marrow from Ly5-b-congenic (C57BL/6) or H2-mismatched (BALB/c) donors. Engraftment was achieved readilymore » in the Ly5-congenic setting, with greater than 80% donor granulocytes and T cells after 0.5 mCi I-131 (estimated 17 Gy to marrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engraftment of H2-mismatched mar row, and engraftment occurred in only 3 of 11 mice receiving 1.5 mCi I-131 delivered by anti-CD45 antibody. Engraftment of H2-mismatched marrow was achieved in 22 of 23 animals receiving 0.75 mCi I-131 delivered by anti-CD45 antibody combined with 8 Gy TBI. Thus, targeted radiation delivered via I-131-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell-depleted H2-mismatched marrow.« less

High-sensitivity virus and mycoplasma screening test reveals high prevalence of parvovirus B19 infection in human synovial tissues and bone marrow.

PubMed

Watanabe, Ken; Otabe, Koji; Shimizu, Norio; Komori, Keiichirou; Mizuno, Mitsuru; Katano, Hisako; Koga, Hideyuki; Sekiya, Ichiro

2018-03-27

Latent microorganism infection is a safety concern for the clinical application of mesenchymal stem cells (MSCs). The aim of this study is to investigate the frequencies and sensitivities of the latent virus and mycoplasma infections in synovium, bone marrow, peripheral blood cells, and blood plasma and cultured synovial MSCs. Total DNA and RNA of the synovium (n = 124), bone marrow (n = 123), peripheral blood cells (n = 121), plasma (n = 121), and 14-day cultured synovial MSCs (n = 63) were collected from patients who underwent total knee arthroplasty or anterior ligament reconstruction after written informed consents were obtained. The multiplex polymerase chain reaction (PCR) primers were designed to quantitatively measure the representative genomes of 13 DNA viruses, 6 RNA viruses, and 9 mycoplasmas. Multi-spliced mRNA detection and virus spike test were also performed to demonstrate the sensitivity of synovial MSCs to the candidate pathogens. In synovium and bone marrow, the positive rates of parvovirus B19 genome were significantly higher than in peripheral blood cells (18.7% and 22% vs. 0.8%, respectively). Multi-alignment analysis of amplified and sequenced viral target genes showed the proximity of the parvovirus B19 gene from different tissue in the same patients. Synovial MSCs cultured for 14 days were positive for virus infection only in two patients (2/62 = 3%). Parvovirus B19 multi-spliced mRNAs were not detected in these two samples. Virus spike test demonstrated the sensitivity of synovial MSCs to herpes simplex virus (HSV)1 and cytomegalovirus (CMV), but not to parvovirus B19. This study revealed a relatively high incidence of latent parvovirus B19 in synovium and bone marrow tissue.

Stromal and Hematopoietic Progenitors from C57/BI/6N Murine Bone Marrow After 30-Day "BION-M1" Spaceflight.

PubMed

Markina, Elena; Andreeva, Elena; Andrianova, Irina; Sotnezova, Elena; Buravkova, Ludmila

2018-05-02

Elucidation of the spaceflight (SF) effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this was provided by project "BION-M1". The purpose of this study was to evaluate the effects of 30-day SF on biosatellite, 7-day recovery (SFR), and subsequent ground control (GC) experiment on the mononuclear cells (MNCs) from C57/BI/6N murine tibia bone marrow. Also, hematopoietic and stromal precursor functions were characterized ex vivo. There was no significant difference in the total MNC number between experimental groups. After SF, immunophenotyping revealed an increase of large-sized CD45 + MNCs corresponded to committed hematopoietic progenitors. The total hematopoietic colony-forming unit (CFU) number decreased after SF and did not restore after 7 day of recovery due to predominant reduction of bi- and multipotent CFUs and primitive burst-forming units in favor of unipotent CFUs. Functional activity of stromal precursors in vitro was only slightly altered. SF cells displayed the enhanced expression of alkaline phosphatase. The data of the GC experiment demonstrated the preservation of the functional activity of progenitor cells from mice bone marrow. The activation of erythropoiesis in expense of burst-forming units of erythrocytes elevation was detected. After 7 days of recovery, the number of colony-forming units of fibroblast (CFUs-f) was similar to the vivarium control, while the proliferative activity of bone marrow stromal precursors decreased. The present study demonstrated that certain hematopoietic progenitors are susceptible to SF factors, while the stromal precursors displayed a certain degree of resistance. These data indicate mild and reversible alterations of bone marrow progenitors after SF.

Multi-institutional Feasibility Study of a Fast Patient Localization Method in Total Marrow Irradiation With Helical Tomotherapy: A Global Health Initiative by the International Consortium of Total Marrow Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Yutaka; Vagge, Stefano; Agostinelli, Stefano

2015-01-01

Purpose: To develop, characterize, and implement a fast patient localization method for total marrow irradiation. Methods and Materials: Topographic images were acquired using megavoltage computed tomography (MVCT) detector data by delivering static orthogonal beams while the couch traversed through the gantry. Geometric and detector response corrections were performed to generate a megavoltage topogram (MVtopo). We also generated kilovoltage topograms (kVtopo) from the projection data of 3-dimensional CT images to reproduce the same geometry as helical tomotherapy. The MVtopo imaging dose and the optimal image acquisition parameters were investigated. A multi-institutional phantom study was performed to verify the image registration uncertainty. Forty-fivemore » MVtopo images were acquired and analyzed with in-house image registration software. Results: The smallest jaw size (front and backup jaws of 0) provided the best image contrast and longitudinal resolution. Couch velocity did not affect the image quality or geometric accuracy. The MVtopo dose was less than the MVCT dose. The image registration uncertainty from the multi-institutional study was within 2.8 mm. In patient localization, the differences in calculated couch shift between the registration with MVtopo-kVtopo and MVCT-kVCT images in lateral, cranial–caudal, and vertical directions were 2.2 ± 1.7 mm, 2.6 ± 1.4 mm, and 2.7 ± 1.1 mm, respectively. The imaging time in MVtopo acquisition at the couch speed of 3 cm/s was <1 minute, compared with ≥15 minutes in MVCT for all patients. Conclusion: Whole-body MVtopo imaging could be an effective alternative to time-consuming MVCT for total marrow irradiation patient localization.« less

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.

Transforming growth factor (TGF. beta. ) decreases the proliferation of human bone marrow fibroblasts by inhibiting the platelet-derived growth factor (PDGF) binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryckaert, M.C.; Tobelem, G.; Lindroth, M.

1988-12-01

Human bone marrow fibroblasts were cultivated and characterized by immunofluorescent staining and electron microscopy. Their interactions with PDGF and TGF{beta} were studied. While a positive intracellular antifibronectin staining was observed, the cultured cells were not labeled with specific antibodies toward factor VIII von Willebrand factor (F VIII/vWF), desmin, and macrophage antigen. The binding of pure human PDGF to the cultured bone marrow fibroblasts was investigated. Addition of an excess of unlabeled PDGF decreased the binding to 75 and 80%, which means that the nonspecific binding represented 20-25% of total binding, whereas epidermal growth factor (EGF) had no effect. Two classesmore » of sites were detected by Scatchard analysis. The stimulation of DNA synthesis of PDGF was quantified by ({sup 3}H)thymidine incorporation. The results suggested that PDGF and TGF{beta} could modulate the growth of bone marrow fibroblasts.« less

Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat

NASA Astrophysics Data System (ADS)

Ghasemnezhad Targhi, Reza; Homayoun, Mansour; Mansouri, Somaieh; Soukhtanloo, Mohammad; Soleymanifard, Shokouhozaman; Seghatoleslam, Masoumeh

2017-01-01

Ionizing radiation by producing free radicals induces tissue oxidative stress and has clastogenic and cytotoxic effects. The radio protective effect of black mulberry extract (BME) has been investigated on liver tissue and bone marrow cells in the rat. Intraperitoneal (ip) administration of 200 mg/kg BME three days before and three days after 3 Gy and 6 Gy gamma irradiation significantly reduced the frequencies of micro nucleated polychromatic erythrocytes (MnPCEs) and micro nucleated norm chromatic erythrocyte (MnNCEs) and increased PCE/PCE+NCE ratio in rat bone marrow compared to the non-treated irradiated groups. Moreover, this concentration of BME extract decreased the level of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as enhanced the total thiol content and catalase activity in rat's liver compared to the non-treated irradiated groups. It seems that BME extract with antioxidant activity reduced the genotoxicity and cytotoxicity induced by gamma irradiation in bone marrow cells and liver in the rat.

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 Gymore » 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.« less

[Descriptive study of activity of the bone marrow donor registry and bank from the Murcia Region (southeast of Spain) (1994-2004)].

PubMed

Rojas Montero, G M; Alvarez López, M R; López Bermejo, A; Moya Quiles, M R; Muro Amador, M

2006-11-01

To perform a descriptive study of the activity of the Bank of marrow donors from Murcia Region. All donors in the Bank of bone marrow from 1994 until 2004 (n=3137). This study analysed the number of donors, their origin and, performed donor searches activity. Donors were typed by serological microlymphocytotoxicity and molecular PCR-SSO and PCR-SSP techniques. The Bank of bone marrow has 3,137 voluntary donors typed in low- and high-resolution. A total of 680 donor searches have been realized. The origin of the donors according to several Areas of Health in which the Autonomous Community of Murcia is divided, is the following one: Area I (28%), Area II (18 %), Area III (23 %), Area IV (6 %), Area VI (10 %) and other provinces (12%). An increase is observed in the number of annual donors as well as an increase very marked of donor searches that are realized every year, especially in 2004.

Analysis of bone marrow plasma cells in patients with solitary bone plasmacytoma.

PubMed

Bhaskar, Archana; Gupta, Ritu; Sharma, Atul; Kumar, Lalit; Jain, Paresh

Local radiotherapy is the treatment of choice for solitary bone plasmacytoma (SBP) and the role of adjuvant systemic chemotherapy in preventing progression to multiple myeloma (MM) is controversial. The purpose of this study was to examine the presence of systemic disease in the form of neoplastic plasma cells (PC) in bone marrow of patients with SBP. Flow cytometric immunophenotyping of PC was carried out on bone marrow aspirate of 7 patients using monoclonal antibodies: CD19 FITC, CD45 FITC, CD20 FITC, CD52 PE, CD117 PE, CD56 PE, CD38 PerCP-Cy5.5, CD138 APC, anti-kappa (κ) FITC and anti-lambda (λ) PE. The neoplastic as well as normal PC were identified in bone marrow aspirate of all the patients at the time of diagnosis; the neoplastic PC ranged from 0.1%to 0.7% of all BM cells and 33.5% to 89.7% of total BMPC. The κ:λ ratio was normal in all the samples ranging from 0.5% to 1.6%. The present work shows the presence of systemic disease in the form of neoplastic PC in bone marrow of patients with SBP. Prospective studies would be required to study if the levels of neoplastic PC in the bone marrow may help us identify patients who are likely to progress to overt MM and benefit from systemic chemotherapy.

HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS

PubMed Central

Rapaport, F. T.; Watanabe, K.; Cannon, F. D.; Mollen, N.; Blumenstock, D.; Ferrebee, J. W.

1972-01-01

17 Cooperstown beagles of known DL-A genotypes were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A-identical donor; 11 littermate and 6 nonlittermate donor-recipient pairs were studied. The recipients are surviving uneventfully for 315, 364, 424, 440, 531, 531, 584, 605, 625, 635, and 649 days in the littermate group and for 211, 279, 280, 368, 479, and 480 days in the nonlittermate group. The radiation chimeras underwent bilateral nephrectomy and received a kidney allograft obtained from their respective marrow donor within 43–120 days after bone marrow transplantation. The renal allografts are surviving for 191, 200, 221, 234, 313, 349, 361, 377, 378, 405, 441, 444, 482, 557, 580, 581, and 586 days, respectively. 12 of 13 skin allografts obtained from the marrow donor are at present surviving in the recipients for 107, 110, 110, 110, 116, 122, 128, 143, 143, 162, 178, and 199 days, respectively; one graft was rejected at 84 days. In contrast, the radiation chimeras rejected 25 skin allografts obtained from DL-A-incompatible donors within 10.5–21 days (MST = 15.2 days). Skin transplants obtained from DL-A-identical siblings of the bone marrow donors were rejected within 20–36 days (MST = 25.8 days) in recipients of bone marrow cells obtained from littermate donors. Recipients of nonlittermate bone marrow transplants accorded such allografts a prolonged survival time of 27–76 days (MST = 56.2 days). Prospective selection of genotypically DL-A-identical donor-recipient pairs results in the regularly reproducible long-term survival of bone marrow allografts. The radiation chimeras produced in this manner have developed a donor-specific state of unresponsiveness to kidney and skin allografts. The results are consistent with the existence in the canine species of at least three closely linked genetic systems relevant to transplantation, including DL-A, MLC, and a possible bone marrow transplantation locus. PMID:4404277

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deeg, H.J.; Storb, R.; Weiden, P.L.

1981-11-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs diedmore » from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.« less

[Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow].

PubMed

Sun, Qi; Chen, Zhenping; Liu, Enbin; Li, Zhanqi; Yang, Qingying; Sun, Fujun; Ma, Yue; Zhang, Hongju; Zhang, Peihong; Ru, Kun

2015-02-01

To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL). A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases. Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases. The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

Cigarette Smoke Inhibits Recruitment of Bone-Marrow-Derived Stem cells to The Uterus

PubMed Central

Zhou, Yuping; Gan, Ye; Taylor, Hugh S.

2011-01-01

Cigarette smoking leads to female infertility and a decreased incidence of endometriosis. Bone marrow derived stem cells are recruited to uterine endometrium and endometriosis. The effect of cigarette smoking on stem cell recruitment to any organ is uncharacterized. We hypothesized that bone marrow-derived mesenchymal stem cell recruitment to the uterus and differentiation would be diminished by cigarette smoke. We used human mesenchymal stem cells (hMSC) in vitro and a mouse model of cigarette smoke exposure. After myeloablation female C57BL/6J received bone marrow cells from males. Mice were exposed to room air or smoke from unfiltered cigarettes. Immunofluorescence and Y-FISH was performed on uterine sections. In vitro hMSCs were treated with 8-Br-cAMP to induce endometrial cell differentiation with or without cigarette smoke extract (CSE) and decidualization assessed morphologically and by prolactin expression. After 4 weeks the total number of Y-chromosome cells in the uterus was reduced by 68% in the smoke exposed mice. Both leukocytes and bone marrow derived endometrial cells were reduced by 60% and 73%, respectively. Differentiation of bone marrow derived cell to endometrial epithelial cells was reduced by 84%. hMSC treated with CSE failed to show cytological characteristics of decidualization. mRNA levels of the decidualization marker prolactin were decreased by 90% in CSE treated cells. Smoking inhibits both recruitment of bone marrow derived stem cells to uterus and stem cell differentiation. Inhibition of stem cells recruitment may be a general mechanism by which smoking leads to long term organ damage through inability to repair or regenerate multiple tissues. PMID:20955787

Characterization of Fatty Acid Composition in Bone Marrow Fluid From Postmenopausal Women: Modification After Hip Fracture.

PubMed

Miranda, Melissa; Pino, Ana María; Fuenzalida, Karen; Rosen, Clifford J; Seitz, Germán; Rodríguez, J Pablo

2016-10-01

Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65-80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. J. Cell. Biochem. 117: 2370-2376, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hematopoietic stem cell transplantation in Europe 1998.

PubMed

Gratwohl, A; Passweg, J; Baldomero, H; Hermans, J; Urbano-Ispizua, A

2000-01-01

Transplantation of hematopoietic stem cells from blood or bone marrow has become accepted therapy for many diseases. Numbers of transplants have increased significantly and stem cell source, donor type and indications have changed during this decade. Information on these changes is essential for interpretation of current data, patient counseling and health care planning. Since 1990, members of the European Group for Blood and Marrow Transplantation and teams known to perform blood or marrow transplants have been invited annually to report their transplant numbers by indication, donor type and stem cell source. Data from these surveys have been used to present data for 1998, to assess current status and to give numbers of transplants per participating country, coefficients of variation between countries for individual indications and changes in indication, stem cell source and donor type over the past decade. In 1998, a total of 20 892 transplants were performed by 528 teams in 31 European countries. Of these transplants 18 400 were first transplants, 5308 (29%) were allogenic, and 13 092 (71%) were autologous. Of the autologous transplants, 809 (6%) were bone marrow derived, and 12 283 (94%) were from peripheral blood stems cells. Of the allogeneic transplants, 3372 (64%) were bone marrow derived, and 1936 (36%) were peripheral blood stem cell transplants. In 1990, the respective figures were 2137 allogeneic (50%) and 2097 (50%) autologous transplants, all exclusively bone marrow derived. Main indications in 1998 were leukemias with 6015 transplants (33%), 68% thereof allogeneic transplants; lymphomas with 7492 transplants (41%), 94% thereof autologous transplants; solid tumors with 4025 transplants (22%), 99% thereof autologous transplants; non-malignant disorders with 868 transplants (5%), 80% thereof allogeneic transplants. Absolute numbers of transplants per year did increase from 4234 in 1990 to 20 892 in 1998. Increase is higher for autologous, than for allogeneic transplants. There were differences in absolute or relative increase over time for individual indications. Transplant rates per number of inhabitants varied between countries, ranging from 0 to >500 total transplants per 10 million inhabitants with a clear correlation between number of teams and transplants per 10 million inhabitants (r=0.61, P<0.001). The least variation between countries was observed for acute leukemias, chronic myeloid leukemia and severe aplastic anemia in allogeneic transplants, for Hodgkin's disease and non-Hodgkin's lymphoma in autologous transplants. These data reflect the current status of blood and marrow transplantation in Europe. They show the continuing increase in utilization, highlight the change from bone marrow to blood as stem cell source and give an objective assessment on presence or absence of trends.

Platelet bioreactor-on-a-chip

PubMed Central

Mazutis, Linas; Wu, Stephen; Sylman, Joanna L.; Ehrlicher, Allen; Machlus, Kellie R.; Feng, Qiang; Lu, Shijiang; Lanza, Robert; Neeves, Keith B.; Weitz, David A.; Italiano, Joseph E.

2014-01-01

Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs. PMID:25606631

Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

NASA Astrophysics Data System (ADS)

Rőszer, Tamás; Pintye, Éva; Benkő, Ilona

2008-12-01

Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

Assessment of functional liver reserve: old and new in 99mTc-sulfur colloid scintigraphy.

PubMed

Matesan, Manuela M; Bowen, Stephen R; Chapman, Tobias R; Miyaoka, Robert S; Velez, James W; Wanner, Michele F; Nyflot, Matthew J; Apisarnthanarax, Smith; Vesselle, Hubert J

2017-07-01

A semiquantitative assessment of hepatic reticuloendothelial system function using colloidal particles scintigraphy has been proposed previously as a surrogate for liver function evaluation. In this article, we present an updated method for the overall assessment of technetium-99m (Tc)-sulfur colloid (SC) biodistribution that combines information from planar and attenuation-corrected Tc-SC single-photon emission computed tomography (SPECT) images. The imaging protocol described here was developed as an easy-to-implement method to assess overall and regional liver function changes associated with chronic liver disease. Thirty patients with chronic liver disease and primary liver cancers underwent Tc-SC whole-body planar imaging and upper-abdomen SPECT/computed tomography (CT) imaging before external beam radiation therapy. Liver plus spleen and bone marrow counts as a fraction of whole-body total counts were calculated from SC planar imaging. Attenuation correction Tc-SC images were rigidly coregistered with treatment planning CT images that contained liver and spleen regions-of-interest. Ratios of total liver counts to total spleen counts were obtained from the aligned Tc-SC SPECT and CT images, and were subsequently used to separate liver plus spleen counts obtained on the planar images. This hybrid SPECT/CT and planar scintigraphy approach yielded an updated estimation of whole-body SC distribution. These biodistribution estimates were compared with historical data for reference. Statistical associations of Tc-SC biodistribution to liver function parameters and liver disease scoring systems (Child-Pugh) were evaluated by Spearman rank correlation. Percentages of Tc-SC uptake ranged from 19.3 to 77.3% for the liver; 3.4 to 40.7% for the spleen; and 19.0 to 56.7% for the bone marrow. Spearman's correlation coefficient showed a significant statistical association between Child-Pugh score and bone marrow uptake at 0.55 (P≤0.05), liver uptake at 0.71 (P≤0.001), spleen uptake at 0.56 (P≤0.05), and spleen plus bone marrow uptake at 0.71 (P≤0.001). There was also a good correlation of SC uptake percentages with individual quantitative liver function components such as albumin and total bilirubin, and qualitative liver function components (varices, portal hypertension, ascites). For albumin: r=0.64 (P<0.001) compared with liver uptake percentage from the whole-body counts, r=0.49 (P<0.001) compared with splenic uptake percentage, and r=0.45 (P≤0.05) compared with bone marrow uptake percentage. We describe a novel liver function quantitative assessment method that combines whole-body planar images and SPECT/CT attenuation-corrected images of Tc-SC distribution. Attenuation-corrected SC images provide valuable regional liver function information, which is a unique feature compared with other imaging methods available. The results of our study indicate that the Tc-SC uptake by the liver, spleen, and bone marrow correlates with liver function parameters in patients with diffuse liver disease and the correlation with liver disease severity is slightly better for liver uptake percentages than for individual values of bone marrow and spleen uptake percentages.

[Soil organic carbon mineralization of Black Locust forest in the deep soil layer of the hilly region of the Loess Plateau, China].

PubMed

Ma, Xin-Xin; Xu, Ming-Xiang; Yang, Kai

2012-11-01

The deep soil layer (below 100 cm) stores considerable soil organic carbon (SOC). We can reveal its stability and provide the basis for certification of the deep soil carbon sinks by studying the SOC mineralization in the deep soil layer. With the shallow soil layer (0-100 cm) as control, the SOC mineralization under the condition (temperature 15 degrees C, the soil water content 8%) of Black Locust forest in the deep soil layer (100-400 cm) of the hilly region of the Loess Plateau was studied. The results showed that: (1) There was a downward trend in the total SOC mineralization with the increase of soil depth. The total SOC mineralization in the sub-deep soil (100-200 cm) and deep soil (200-400 cm) were equivalent to approximately 88.1% and 67.8% of that in the shallow layer (0-100 cm). (2) Throughout the carbon mineralization process, the same as the shallow soil, the sub-deep and deep soil can be divided into 3 stages. In the rapid decomposition phase, the ratio of the mineralization or organic carbon to the total mineralization in the sub-deep and deep layer (0-10 d) was approximately 50% of that in the shallow layer (0-17 d). In the slow decomposition phase, the ratio of organic carbon mineralization to total mineralization in the sub-deep, deep layer (11-45 d) was 150% of that in the shallow layer (18-45 d). There was no significant difference in this ratio among these three layers (46-62 d) in the relatively stable stage. (3) There was no significant difference (P > 0.05) in the mineralization rate of SOC among the shallow, sub-deep, deep layers. The stability of SOC in the deep soil layer (100-400 cm) was similar to that in the shallow soil layer and the SOC in the deep soil layer was also involved in the global carbon cycle. The change of SOC in the deep soil layer should be taken into account when estimating the effects of soil carbon sequestration in the Hilly Region of the Loess Plateau, China.

Effect of subalpine canopy removal on snowpack, soil solution, and nutrient export, Fraser Experimental Forest, CO

USGS Publications Warehouse

Stottlemyer, R.; Troendle, C.A.

1999-01-01

Research on the effects of vegetation manipulation on snowpack, soil water, and streamwater chemistry and flux has been underway at the Fraser Experimental Forest (FEF), CO, since 1982. Greater than 95% of FEF snowmelt passes through watersheds as subsurface flow where soil processes significantly alter meltwater chemistry. To better understand the mechanisms accounting for annual variation in watershed streamwater ion concentration and flux with snowmelt, we studied subsurface water flow, its ion concentration, and flux in conterminous forested and clear cut plots. Repetitive patterns in subsurface flow and chemistry were apparent. Control plot subsurface flow chemistry had the highest ion concentrations in late winter and fall. When shallow subsurface flow occurred, its Ca2+, SO42-, and HCO3- concentrations were lower and K+ higher than deep flow. The percentage of Ca2+, NO3-, SO42-, and HCO3- flux in shallow depths was less and K+ slightly greater than the percentage of total flow. Canopy removal increased precipitation reaching the forest floor by about 40%, increased peak snowpack water equivalent (SWE) > 35%, increased the average snowpack Ca2+, NO3-, and NH4+ content, reduced the snowpack K+ content, and increased the runoff four-fold. Clear cutting doubled the percentage of subsurface flow at shallow depths, and increased K+ concentration in shallow subsurface flow and NO3- concentrations in both shallow and deep flow. The percentage change in total Ca2+, SO42-, and HCO3- flux in shallow depths was less than the change in water flux, while that of K+ and NO3- flux was greater. Relative to the control, in the clear cut the percentage of total Ca2+ flux at shallow depths increased from 5 to 12%, SO42- 5.4 to 12%, HCO3- from 5.6 to 8.7%, K+ from 6 to 35%, and NO3- from 2.7 to 17%. The increases in Ca2+ and SO42- flux were proportional to the increase in water flux, the flux of HCO3- increased proportionally less than water flux, and NO3- and K+ were proportionally greater than water flux. Increased subsurface flow accounted for most of the increase in non-limiting nutrient loss. For limiting nutrients, loss of plant uptake and increased shallow subsurface flow accounted for the greater loss. Seasonal ion concentration patterns in streamwater and subsurface flow were similar.Research on the effects of vegetation manipulation on snowpack, soil water, and streamwater chemistry and flux has been underway at the Fraser Experimental Forest (FEF), CO, since 1982. Greater than 95% of FEF snowmelt passes through watersheds as subsurface flow where soil processes significantly alter meltwater chemistry. To better understand the mechanisms accounting for annual variation in watershed streamwater ion concentration and flux with snowmelt, we studied subsurface water flow, its ion concentration, and flux in conterminous forested and clear cut plots. Repetitive patterns in subsurface flow and chemistry were apparent. Control plot subsurface flow chemistry had the highest ion concentrations in late winter and fall. When shallow subsurface flow occurred, its Ca2+, SO42-, and HCO3- concentrations were lower and K+ higher than deep flow. The percentage of Ca2+, NO3-, SO42-, and HCO3- flux in shallow depths was less and K+ slightly greater than the percentage of total flow. Canopy removal increased precipitation reaching the forest floor by about 40%, increased peak snowpack water equivalent (SWE) > 35%, increased the average snowpack Ca2+, NO3-, and NH4+ content, reduced the snowpack K+ content, and increased the runoff four-fold. Clear cutting doubled the percentage of subsurface flow at shallow depths, and increased K+ concentration in shallow subsurface flow and NO3- concentrations in both shallow and deep flow. The percentage change in total Ca2+, SO42-, and HCO3- flux in shallow depths was less than the change in water flux, while that of K+ and NO3- flux was greater. Relative to the control, in the clear cut the percentage of total Ca

Concentrations and potential health hazards of organochlorine pesticides in (shallow) groundwater of Taihu Lake region, China.

PubMed

Wu, Chunfa; Luo, Yongming; Gui, Tong; Huang, Yujuan

2014-02-01

A total of 27 shallow groundwater samples were collected from the Taihu Lake region (TLR), to determine the concentrations of 14 organochlorine pesticide (OCP) species, identify their possible sources, and estimate health risk of drinking the shallow groundwater. All OCP species occurred in the shallow groundwater of TLR with high detection frequency except p, p'-dichlorodiphenyldichlorothane (p, p'-DDD) and p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT). DDTs and hexachlorocyclohexanes (HCHs) were the dominant OCP contaminants in the shallow groundwater of TLR, and they account for 44.2% total OCPs. The low α-HCH/γ-HCH ratio, high β-HCH/(α+γ)-HCH ratio and β-HCH being the dominant HCH isomers for the majority of samples suggest that the HCHs were mainly from the historical use of lindane after a period of degradation. p, p'-DDE being the dominant DDT metabolite for all the samples indicated that the DDTs were mainly from the historical residues. Compositional analysis also suggested that there were fresh input sources of heptachlors, aldrins and endrins in addition to the historical residues. Correlation analysis indicated the hexachlorobenzene (HCB) impurity in the shallow groundwater of TLR was likely from the historical application of lindane and technical HCH (a mixture of HCH isomers that is produced by photochlorination of benzene). Carcinogenic risk values for α-HCH, heptachlor, heptachlor epoxide, aldrins and dieldrin in the shallow groundwater in majority area of TLR were found to be >10(-6), posing a potentially serious cancer risk to those dependant on shallow groundwater for drinking water. © 2013.

Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell Transplants Performed in Australia and New Zealand: A Study from the Australasian Bone Marrow Transplant Recipient Registry.

PubMed

Patton, William Nigel; Nivison-Smith, Ian; Bardy, Peter; Dodds, Anthony; Ma, David; Shaw, Peter John; Kwan, John; Wilcox, Leonie; Butler, Andrew; Carter, John M; Blacklock, Hilary; Szer, Jeffrey

2017-01-01

A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Use of reinforced soil foundation (RSF) to support shallow foundation.

DOT National Transportation Integrated Search

2008-11-01

This research study aims at investigating the potential benefits of using reinforced soil foundations to improve the bearing capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 tests, includ...

Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy.

PubMed

Whitney, Daniel G; Singh, Harshvardhan; Miller, Freeman; Barbe, Mary F; Slade, Jill M; Pohlig, Ryan T; Modlesky, Christopher M

2017-01-01

Nonambulatory children with severe cerebral palsy (CP) have underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. Ambulatory children with mild spastic CP and typically developing children (4 to 11years; 12/group) were compared. Magnetic resonance imaging was used to estimate cortical bone, bone marrow and total bone volume and width, bone strength [i.e., section modulus (Z) and polar moment of inertia (J)], and bone marrow fat concentration in the midtibia, and muscle volume, intermuscular, subfascial, and subcutaneous adipose tissue (AT) volume and intramuscular fat concentration in the midleg. Accelerometer-based activity monitors worn on the ankle were used to assess physical activity. There were no group differences in age, height, body mass, body mass percentile, BMI, BMI percentile or tibia length, but children with CP had lower height percentile (19th vs. 50th percentile) and total physical activity counts (44%) than controls (both p<0.05). Children with CP also had lower cortical bone volume (30%), cortical bone width in the posterior (16%) and medial (32%) portions of the shaft, total bone width in the medial-lateral direction (15%), Z in the medial-lateral direction (34%), J (39%) and muscle volume (39%), and higher bone marrow fat concentration (82.1±1.8% vs. 80.5±1.9%), subfascial AT volume (3.3 fold) and intramuscular fat concentration (25.0±8.0% vs. 16.1±3.3%) than controls (all p<0.05). When tibia length was statistically controlled, all group differences in bone architecture, bone strength, muscle volume and fat infiltration estimates, except posterior cortical bone width, were still present (all p<0.05). Furthermore, a higher intermuscular AT volume in children with CP compared to controls emerged (p<0.05). Ambulatory children with mild spastic CP exhibit an underdeveloped bone architecture and low bone strength in the midtibia and a greater infiltration of fat in the bone marrow and surrounding musculature compared to typically developing children. Whether the deficit in the musculoskeletal system of children with CP is associated with higher chronic disease risk and whether the deficit can be mitigated requires further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

Adoptive immunotherapy against allogeneic kidney grafts in dogs with stable hematopoietic trichimerism.

PubMed

Graves, Scott S; Hogan, William J; Kuhr, Christian; Diaconescu, Razvan; Harkey, Michael; Sale, George E; Stone, Brad; Georges, George E; Storb, Rainer

2008-11-01

Dogs given nonmyeloablative conditioning and marrow grafts from 2 dog leukocyte antigen (DLA)-identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. In this study, we used trichimeras to evaluate strategies for adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from 2 DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy of total body irradiation (TBI) and given a short course of postgraft immunosuppression. After stable hematopoietic engraftment was confirmed, a kidney was transplanted from 1 of the 2 marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes from each kidney donor were then used to sensitize the alternate marrow donor. The trichimeric recipients were given donor lymphocyte infusions (DLIs) from the sensitized dogs and monitored for chimerism, graft-versus-host disease (GVHD), and kidney rejection. After DLI, we observed both prompt rejection of the transplanted marrow and donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably due to shared minor histocompatibility antigens, host chimerism also disappeared, and GVHD in skin, gut, and liver developed. The native kidneys, although exhibiting lymphocytic infiltration, remained functionally normal. This study demonstrates that under certain experimental conditions, the kidney--an organ ordinarily not involved in graft-versus-host reactions--can be targeted by sensitized donor lymphocytes.

Adoptive Immunotherapy against Allogeneic Kidney Grafts in Dogs with Stable Hematopoietic Trichimerism

PubMed Central

Graves, Scott S.; Hogan, William J.; Kuhr, Christian; Diaconescu, Razvan; Harkey, Michael; Sale, George E.; Stone, Brad; Georges, George E.; Storb, Rainer

2008-01-01

Dogs given nonmyeloablative conditioning and marrow grafts from two dog leukocyte antigen- (DLA) identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. Here, we used trichimeras to evaluate strategies of adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from two DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy total body irradiation and given a short course of postgrafting immunosuppression. After confirming stable hematopoietic engraftment, a kidney was transplanted from one of the two marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes (PBL) from each kidney donor were then used to sensitize the alternate marrow donor. Donor lymphocyte infusions (DLI) from the sensitized dogs were given to the trichimeric recipients, whereupon chimerism, graft-versus-host disease (GvHD), and kidney rejection were monitored. After DLI, we observed both prompt rejection of the transplanted marrow-donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably, owing to shared minor histocompatibility antigens, host chimerism also disappeared and GvHD in skin, gut, and liver developed. The native kidneys, while showing lymphocytic infiltration, remained functionally normal. The current study demonstrated that under certain experimental conditions, the kidney, an organ ordinarily not involved in graft-versus-host reactions, can be targeted by sensitized donor lymphocytes. PMID:18940673

Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase

PubMed Central

Parry, Erin M.; Alder, Jonathan K.; Qi, Xiaodong; Chen, Julian J.-L.

2011-01-01

Mutations in the essential telomerase components hTERT and hTR cause dyskeratosis congenita, a bone marrow failure syndrome characterized by mucocutaneous features. Some (∼ 3%) sporadic aplastic anemia (AA) and idiopathic pulmonary fibrosis cases also carry mutations in hTERT and hTR. Even though it can affect clinical outcome, because the mutation frequency is rare, genetic testing is not standard. We examined whether the cooccurrence of bone marrow failure and pulmonary fibrosis in the same individual or family enriches for the presence of a telomerase mutation. Ten consecutive individuals with a total of 36 family members who fulfilled these criteria carried a germline mutant telomerase gene (100%). The mean age of onset for individuals with AA was significantly younger than that for those with pulmonary fibrosis (14 vs 51; P < .0001). Families displayed autosomal dominant inheritance and there was an evolving pattern of genetic anticipation, with the older generation primarily affected by pulmonary fibrosis and successive generations by bone marrow failure. The cooccurrence of AA and pulmonary fibrosis in a single patient or family is highly predictive for the presence of a germline telomerase defect. This diagnosis affects the choice of bone marrow transplantation preparative regimen and can prevent morbidity. PMID:21436073

(18)F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate.

PubMed

Sachpekidis, Christos; Mai, Elias K; Goldschmidt, Hartmut; Hillengass, Jens; Hose, Dirk; Pan, Leyun; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-06-01

The value of F-FDG PET in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the kinetics of F-FDG in the bone marrow and extramedullary sites in MM. This study aimed to evaluate quantitative data on kinetics and distribution patterns of F-FDG in MM patients with regard to pelvic bone marrow plasma cell infiltration. The study included 40 patients with primary MM. Dynamic PET/CT scanning of the lower lumbar spine and pelvis was performed after the administration of F-FDG. Whole-body PET/CT studies were performed. Sites of focal increased tracer uptake were considered as highly suggestive of myelomatous involvement after taking into account the patient history and CT findings. Bone marrow of the os ilium without pathologic tracer accumulation served as reference. The evaluation of dynamic PET/CT studies was based in addition to the conventional visual (qualitative) assessment, on semiquantitative (SUV) calculations, as well as on absolute quantitative estimations after application of a 2-tissue compartment model and a noncompartmental approach. F-FDG quantitative information and corresponding distribution patterns were correlated with pelvic bone marrow plasma cell infiltration. Fifty-two myelomatous lesions were detected in the pelvis. All parameters in suspected MM lesions ranged in significantly higher levels than in reference tissue (P < 0.01). Correlative analyses revealed that bone marrow plasma cell infiltration rate correlated significantly with SUVaverage, SUVmax, and the parameters K1, influx, and fractal dimension of F-FDG in reference bone marrow (P < 0.01). In addition, whole-body static PET/CT imaging demonstrated 4 patterns of tracer uptake; these are as follows: negative, focal, diffuse, and mixed (focal/diffuse) tracer uptake. Patients with a mixed pattern of radiotracer uptake had the highest mean plasma cell infiltration rate in their bone marrow, whereas those with negative PET/CT scans demonstrated the lowest bone marrow plasma cell infiltration. In total, 265 focal myeloma-indicative F-FDG-avid lesions were detected, 129 of which correlated with low-dose CT osteolytic findings. No significant correlation between the number of focal lesions detected in PET/CT and bone marrow infiltration was detected. The F-FDG kinetic parameters K1, influx, and fractal dimension as well as SUVaverage from reference tissue correlated significantly with bone marrow malignant plasma cell infiltration rate. Patients with negative PET/CT demonstrated the lowest bone marrow infiltration by malignant plasma cells, whereas those with a mixed pattern of tracer uptake had the highest infiltration.

Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onoe, K.; Good, R.A.; Yamamoto, K.

1986-06-01

Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, (BR----AKR), as well as syngeneic marrow cells, (AKR----AKR), showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice thatmore » had total or partial histoincompatibility at the H-2 determinants between donor and recipient, (B10----AKR), (B10.AQR----AKR), (B10.A(4R)----AKR), or (B10.A(5R)----AKR), were almost completely unresponsive in DTH and antibacterial immunity. However, when (B10----AKR) H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type.« less

Long-Term Tolerance Towards Haploidentical Vascularized Composite Allograft Transplantation in a Canine Model Using Bone Marrow or Mobilized Stem Cells

PubMed Central

Chang, Jeff; Graves, Scott S.; Butts-Miwongtum, Tiffany; Sale, George E.; Storb, Rainer; Mathes, David W.

2017-01-01

Background The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen (DLA) identical donor. In the present study, we extend those findings across a DLA mismatched barrier. Methods Eight Recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n=4) or granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (n=4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days). Results In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5–7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease (GVHD) while 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance towards its VCA (>90 weeks). Conclusion The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance towards the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared to marrow HCT and an increase in the incidence of GVHD. PMID:27861292

Identification of Suitable Reference Genes for mRNA Studies in Bone Marrow in a Mouse Model of Hematopoietic Stem Cell Transplantation.

PubMed

Li, H; Chen, C; Yao, H; Li, X; Yang, N; Qiao, J; Xu, K; Zeng, L

2016-10-01

Bone marrow micro-environment changes during hematopoietic stem cell transplantation (HSCT) with subsequent alteration of genes expression. Quantitative polymerase chain reaction (q-PCR) is a reliable and reproducible technique for the analysis of gene expression. To obtain more accurate results, it is essential to find a reference during HSCT. However, which gene is suitable during HSCT remains unclear. This study aimed to identify suitable reference genes for mRNA studies in bone marrow after HSCT. C57BL/6 mice were treated with either total body irradiation (group T) or busulfan/cyclophosphamide (BU/CY) (group B) followed by infusion of bone marrow cells. Normal mice without treatments were served as a control. All samples (group T + group B + control) were defined as group G. On days 7, 14, and 21 after transplantation, transcription levels of 7 candidate genes, ACTB, B2M, GAPDH, HMBS, HPRT, SDHA, and YWHAZ, in bone marrow cells were measured by use of real-time quantitative PCR. The expression stability of these 7 candidate reference genes were analyzed by 2 statistical software programs, GeNorm and NormFinder. Our results showed that ACTB displayed the highest expression in group G, with lowest expression of PSDHA in group T and HPRT in groups B and G. Analysis of expression stability by use of GeNorm or NormFinder demonstrated that expression of B2M in bone marrow were much more stable during HSCT, compared with other candidate genes including commonly used reference genes GAPDH and ACTB. ACTB could be used as a suitable reference gene for mRNA studies in bone marrow after HSCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org; Debernardo, Robert; Radivoyevitch, Tomas

Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile,more » 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.« less

Use of reinforced soil foundation (RSF) to support shallow foundation : summary report, November 2008.

DOT National Transportation Integrated Search

2008-05-01

This research study investigates the potential benefits of using reinforced soil foundations to improve the bearing : capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 : tests, including 3...

Use of reinforced soil foundation (RSF) to support shallow foundation : summary report.

DOT National Transportation Integrated Search

2008-05-01

This research study investigates the potential benefits of using reinforced soil foundations to improve the bearing capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 tests, including 38 la...

Cyclic, low-dose total body irradiation for metastatic neuroblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Angio, G.J.; Evans, A.E.

1983-12-01

Total body irradiation (TBI) can be thought of as a systemic anticancer agent. It therefore might best be given like an adjuvant drug, i.e., in tolerable doses, cyclically. The therapeutic ratio between normal bone marrow stem cells and suitably sensitive cancer cells should be widened by these means. Fourteen children with advanced (Stage IV) neuroblastomas were given 100-150 rad TBI in 50 rad daily fractions along with each three-week cycle of standard triple-agent chemotherapy (vincristine, DTIC, cyclophosphamide). Two patients died of toxicity and one is still undergoing therapy. Four of the remaining 12 survive free of disease for 12+ tomore » 31+ months. The regimen is well tolerated, but prolonged, pronounced bone marrow depression, especially thrombocytopenia, commonly occurs after doses of 300-450 rad.« less

Paternity after bone marrow transplantation following conditioning with total body irradiation.

PubMed

Pakkala, S; Lukka, M; Helminen, P; Koskimies, S; Ruutu, T

1994-04-01

A 28-year-old man with chronic myeloid leukaemia received an allogeneic bone marrow transplant after conditioning with daunorubicin, cyclophosphamide and fractionated total body irradiation (TBI). Four years later his wife gave birth to a healthy child. Although the patient was azospermic serologic HLA testing suggested that the patient was the father of the child. DNA fingerprinting as well as analysis of three variable number of tandem repeats (VNTR) loci D1S80 (MCT118), D17S30 (YNZ22) and the apolipoprotein B hypervariable region (apo B 3') gave unequivocal results showing that the patient was the father. Fathering a child after TBI-containing regimen has been very rare and this is the first case where the paternity has been proven with DNA methodology.

Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia.

PubMed

Giri, N; Vowels, M R; Barr, A L; Mameghan, H

1992-07-01

We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non-lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI.

G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

NASA Astrophysics Data System (ADS)

Grivtsova, L. Yu; Melkova, K. N.; Kupryshkina, N. A.; Vorotnikov, I. K.; Grigoryeva, T. A.; Selchuk, V. Yu; Grebennikova, O. P.; Titova, G. V.; Tupitsyn, N. N.

2018-01-01

60 samples of G-CSF-primed bone marrow (39 cancer patients and 21 healthy donors) to be used for transplantation to cancer patients were analyzed and compared by main characteristics with historical control and 13 bone marrow samples from control patient with mastopathy. Basing on morphological and multicolor flow cytometry findings certain characteristics of G-CSF-primed bone marrow were discovered, such as a significant increase in blast count in cancer patients as compared to donors and control patients (p<0.037), a higher neutrophil maturation index (p<0.001) and a lower percentage of mature lymphocytes (p<0.008) as compared to the control group. Among lymphocyte populations G-CSF-priming was associated with a significant increase in the total of mature CD3+ T-cells and CD8+ T-killers (p<0.0001) and a decrease in CD56+CD3- and/or CD16+CD3- NK-cells (p<0.006) both in cancer patients and healthy donors in comparison with the controls.

Osteonecrosis of the hip in patients with aplastic anemia.

PubMed Central

Park, Jeongmi; Jun, Jeongsu; Kim, Yongsik; Lee, Jongwook; Kim, Chunchu; Hahn, Seongtae

2002-01-01

The incidence and clinical and magnetic resonance imaging features of osteonecrosis of the hip were evaluated in patients with aplastic anemia. Two hundred and forty-one patients with aplastic anemia were examined using MR imaging of bone marrow during the five years from 1994 to 1998. Osteonecrosis of the hip was observed on MR imaging in nineteen (15 males and 4 females, mean age 35 yr) of the 241 patients. It was present in both hips in 14 patients, and there were five cases with unilateral occurrence, with a total of 33 involved hips. All except for five hips with associated bone marrow edema revealed increased fatty marrow conversion in the proximal femoral metaphysis. In nine patients, osteonecrosis was detected without any pain. Five patients already had osteonecrosis before any medication was administered. Twelve patients received antilymphocyte globulin, and seven patients received a low dose of steroids before the MR diagnosis of osteonecrosis. Osteonecrosis of the hip frequently develops in patients with aplastic anemia (7.9%), associated with fatty marrow conversion of the proximal femoral metaphysis. PMID:12483006

Viridans streptococcal shock syndrome during bone marrow transplantation.

PubMed

Martino, R; Manteiga, R; Sánchez, I; Brunet, S; Sureda, A; Badell, I; Argilés, B; Subirá, M; Bordes, R; Domingo-Albós, A

1995-01-01

Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia. Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation). All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant. Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation. All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS. These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.

Use of reinforced soil foundation (RSF) to support shallow foundation : final report, November 2008.

DOT National Transportation Integrated Search

2008-11-01

This research study aims at investigating the potential benefits of using reinforced soil foundations to improve the bearing capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 tests, includ...

Analysis of shallow-groundwater dynamic responses to water supply change in the Haihe River plain

NASA Astrophysics Data System (ADS)

Lin, Z.; Lin, W.; Pengfei, L.

2015-05-01

When the middle route of the South-to-North Water Diversion Project is completed, the water supply pattern of the Haihe River plain in North China will change significantly due to the replenishment of water sources and groundwater-exploitation control. The water-cycle-simulation model - MODCYCLE, has been used in simulating the groundwater dynamic balance for 2001-2010. Then different schemes of water supply in 2020 and 2030 were set up to quantitatively simulate the shallow-groundwater dynamic responses in the future. The results show that the total shallow-groundwater recharge is mainly raised by the increases in precipitation infiltration and surface-water irrigation infiltration. Meanwhile, the decrease of groundwater withdrawal contributes to reduce the total discharge. The recharge-discharge structure of local groundwater was still in a negative balance but improved gradually. The shallow-groundwater level in most parts was still falling before 2030, but more slowly. This study can benefit the rational exploitation of water resources in the Haihe River plain.

Do shallow soil, low water availability, or their combination increase the competition between grasses with different root systems in karst soil?

PubMed

Zhao, Yajie; Li, Zhou; Zhang, Jing; Song, Haiyan; Liang, Qianhui; Tao, Jianping; Cornelissen, Johannes H C; Liu, Jinchun

2017-04-01

Uneven soil depth and low water availability are the key limiting factors to vegetation restoration and reconstruction in limestone soils such as in vulnerable karst regions. Belowground competition will possibly increase under limited soil resources. Here, we investigate whether low resource availability (including shallow soil, low water availability, and shallow soil and low water availability combined) stimulates the competition between grasses with different root systems in karst soil, by assessing their growth response, biomass allocation, and morphological plasticity. In a full three-way factorial blocked design of soil depth by water availability by neighbor identity, we grew Festuca arundinacea (deep-rooted) and Lolium perenne (shallow-rooted) under normal versus shallow soil depth, high versus low water availability, and in monoculture (conspecific neighbor) versus mixture (neighbor of the other species). The key results were as follows: (1) total biomass and aboveground biomass in either of the species decreased with reduction of resources but were not affected by planting patterns (monoculture or mixture) even at low resource levels. (2) For F. arundinacea, root biomass, root mass fraction, total root length, and root volume were higher in mixture than in monoculture at high resource level (consistent with resource use complementarity), but lower in mixture than in monoculture at low resource levels (consistent with interspecific competition). In contrast for L. perenne, either at high or low resource level, these root traits had mostly similar values at both planting patterns. These results suggest that deep-rooted and shallow-rooted plant species can coexist in karst regions under current climatic regimes. Declining resources, due to shallow soil, a decrease in precipitation, or combined shallow soil and karst drought, increased the root competition between plants of deep-rooted and shallow-rooted species. The root systems of deep-rooted plants may be too small to get sufficient water and nutrients from dry, shallow soil, while shallow-rooted plants will maintain a dominant position with their already adaptive strategy in respect of root biomass allocation and root growth.

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats.

PubMed

Zhou, Jing; Jiang, Liyan; Long, Xuan; Fu, Cuiping; Wang, Xiangdong; Wu, Xiaodan; Liu, Zilong; Zhu, Fen; Shi, Jindong; Li, Shanqun

2016-09-01

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on combined acid plus small non-acidified particle (CASP)-induced aspiration lung injury. Enhanced green fluorescent protein (EGFP(+) ) or EGFP(-) BMSCs or 15d-PGJ2 were injected via the tail vein into rats immediately after CASP-induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone-marrow-derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP-induced lung injury. Bone-marrow-derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor-α and Cytokine-induced neutrophil chemoattractant (CINC)-1 and the expression of p-p65 and increased the levels of interleukin-10 and 15d-PGJ2 and the expression of peroxisome proliferator-activated receptor (PPAR)-γ in the lung tissue in CASP-induced rats. Tumour necrosis factor-α stimulated BMSCs to secrete 15d-PGJ2 . A tracking experiment showed that EGFP(+) BMSCs were able to migrate to local lung tissues. Treatment with 15d-PGJ2 also significantly inhibited CASP-induced lung inflammation and the production of pro-inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC-derived 15d-PGJ2 activation of the PPAR-γ receptor, reducing the production of proinflammatory cytokines. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

FLOCK cluster analysis of plasma cell flow cytometry data predicts bone marrow involvement by plasma cell neoplasia.

PubMed

Dorfman, David M; LaPlante, Charlotte D; Li, Betty

2016-09-01

We analyzed plasma cell populations in bone marrow samples from 353 patients with possible bone marrow involvement by a plasma cell neoplasm, using FLOCK (FLOw Clustering without K), an unbiased, automated, computational approach to identify cell subsets in multidimensional flow cytometry data. FLOCK identified discrete plasma cell populations in the majority of bone marrow specimens found by standard histologic and immunophenotypic criteria to be involved by a plasma cell neoplasm (202/208 cases; 97%), including 34 cases that were negative by standard flow cytometric analysis that included clonality assessment. FLOCK identified discrete plasma cell populations in only a minority of cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (38/145 cases; 26%). Interestingly, 55% of the cases negative by standard analysis, but containing a FLOCK-identified discrete plasma cell population, were positive for monoclonal gammopathy by serum protein electrophoresis and immunofixation. FLOCK-identified and quantitated plasma cell populations accounted for 3.05% of total cells on average in cases positive for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria, and 0.27% of total cells on average in cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (p<0.0001; area under the curve by ROC analysis=0.96). The presence of a FLOCK-identified discrete plasma cell population was predictive of the presence of plasma cell neoplasia with a sensitivity of 97%, compared with only 81% for standard flow cytometric analysis, and had specificity of 74%, PPV of 84% and NPV of 95%. FLOCK analysis, which has been shown to provide useful diagnostic information for evaluating patients with suspected systemic mastocytosis, is able to identify neoplastic plasma cell populations analyzed by flow cytometry, and may be helpful in the diagnostic evaluation of bone marrow samples for involvement by plasma cell neoplasia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ji Hyun; Stein, Anthony; Tsai, Nicole

Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph nodemore » chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.« less

Tolerance to Vascularized Composite Allografts in Canine Mixed Hematopoietic Chimeras

PubMed Central

Mathes, David W.; Hwang, Billanna; Graves, Scott S.; Edwards, James; Chang, Jeff; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Nash, Richard A.; Storb, Rainer.

2012-01-01

Background Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a highly reproducible strategy for the induction of tolerance towards solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of highly antigenic vascularized composite allografts. Methods Stable mixed chimerism was established in dogs given a sublethal dose (1–2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 (range 4-54) months after HCT. Results All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted composite tissue grafts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18–29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared to extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared to normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared to non-draining lymph nodes of vascularized composite allografts. Conclusion These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function towards maintenance of the vascularized composite allograft. PMID:22082819

High-resolution axial MR imaging of tibial stress injuries

PubMed Central

2012-01-01

Purpose To evaluate the relative involvement of tibial stress injuries using high-resolution axial MR imaging and the correlation with MR and radiographic images. Methods A total of 33 patients with exercise-induced tibial pain were evaluated. All patients underwent radiograph and high-resolution axial MR imaging. Radiographs were taken at initial presentation and 4 weeks later. High-resolution MR axial images were obtained using a microscopy surface coil with 60 × 60 mm field of view on a 1.5T MR unit. All images were evaluated for abnormal signals of the periosteum, cortex and bone marrow. Results Nineteen patients showed no periosteal reaction at initial and follow-up radiographs. MR imaging showed abnormal signals in the periosteal tissue and partially abnormal signals in the bone marrow. In 7 patients, periosteal reaction was not seen at initial radiograph, but was detected at follow-up radiograph. MR imaging showed abnormal signals in the periosteal tissue and entire bone marrow. Abnormal signals in the cortex were found in 6 patients. The remaining 7 showed periosteal reactions at initial radiograph. MR imaging showed abnormal signals in the periosteal tissue in 6 patients. Abnormal signals were seen in the partial and entire bone marrow in 4 and 3 patients, respectively. Conclusions Bone marrow abnormalities in high-resolution axial MR imaging were related to periosteal reactions at follow-up radiograph. Bone marrow abnormalities might predict later periosteal reactions, suggesting shin splints or stress fractures. High-resolution axial MR imaging is useful in early discrimination of tibial stress injuries. PMID:22574840

Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study

PubMed Central

Casazza, K; Hanks, LJ; Hidalgo, B; Hu, HH; Affuso, O

2011-01-01

Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 minutes of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after ten weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization. PMID:21939791

Characteristics of Leachate and Their Effect on Shallow Groundwater Quality (Case Study : TPA Cipayung, Depok)

NASA Astrophysics Data System (ADS)

Widiastuti, Atika; Hartono, Djoko M.; Moersidik, Setyo S.; Gusniani, Irma

2018-03-01

The problems arising from landfill activity is leaked leachate that is not absorbed well into leachate stabilization pond which furthermore contaminates shallow groundwater around landfill, include Cipayung landfill. The aims of this study is to determine the characteristics of leachate and their effect on shallow groundwater quality around landfill based on temperature, pH, Total Suspended Solids (TSS), Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Total Nitrogen (TN), Mercury (Hg), and fecal coliform. Data were analyzed based on leachate samples at influent point, effluent point, and 7 sampling points of residents’s well with distance variation every 100 meters within 300 meters radius having leachate stabilization pond as benchmark. According to the standard of Indonesia’s Ministry of Environment and Forestry law No. 59 of 2016, the results showed that leachate quality was still above the standard of BOD, COD, and Total Nitrogen parameters; 4178.0 mg/L, 70556.0 mg/L and 373.3 mg/L for influent point, and 3142.0 mg/L, 9055.2 mg/L, and 350 mg/L for the effluent point. Pollution Index of shallow groundwater is between lightly and moderately contaminated. This study showed that the further the distance between sampling point and leachate stabilization pond is, the lower the Polution Index is.

In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, A.M.; Zsebo, K.M.; Inoue, H.

1987-04-01

Osmotic pumps containing Escherichia coli-derived recombinant human granulocyte colony-stimulating factor (rhG-CSF) were attached to indwelling jugular vein catheters and implanted subcutaneously into Golden Syrian hamsters. Within 3 days, peripheral granulocyte counts had increased > 10-fold with a concomitant 4-fold increase in total leukocytes. Microscopic examination of Wright-Giemsa-stained blood smears from rhG-CSF hamsters showed that only the neutrophil subpopulation of granulocytes had increased. After subcutaneous injection at /sup 35/S-labeled rhG-CSF doses of up to 10 ..mu..g x kg/sup -1/ x day/sup -1/ only granulocyte counts were affected. However, at higher dose levels, a transient thrombocytopenia was noted. Erythrocyte and lymphocyte/monocyte countsmore » remained unaffected by rhG-CSF over the entire dose range studied. Total leukocyte counts increased 3-fold within 12 hr after a single s.c. injection of rhG-CSF. This early effect was associated with an increase in the total number of colony-forming cells and the percent of active cycling cells in the marrow. A sustained elevation of peripheral leukocyte and marrow progenitor counts was observed following seven daily s.c. injections of rhG-CSF. The ability of rhG-CSF to increase the production and release of granulocytes from the marrow may underlie the beneficial effect it produced on the restoration of peripheral leukocyte counts in hamsters made leukopenic by treatment with 5-fluorouracil.« less

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion

PubMed Central

Carbonaro, Denise A.; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C.; Dorey, Frederick; Kellems, Rodney E.; Blackburn, Michael R.

2008-01-01

Adenosine deaminase (ADA)–deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose–dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy. PMID:18356486

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.

PubMed

Carbonaro, Denise A; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C; Dorey, Frederick; Kellems, Rodney E; Blackburn, Michael R; Kohn, Donald B

2008-06-15

Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose-dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

Successive transitory distribution of Thaumarchaeota and partitioned distribution of Bathyarchaeota from the Pearl River estuary to the northern South China Sea.

PubMed

Zhou, Zhichao; Zhang, Guo-Xia; Xu, Yan-Bin; Gu, Ji-Dong

2018-06-26

Thaumarchaeota and Bathyarchaeota (formerly named Miscellaneous Crenarchaeotal Group, MCG) are globally occurring archaea playing potential roles in nitrogen and carbon cycling, especially in marine benthic biogeochemical cycle. Information on their distributional and compositional patterns could provide critical clues to further delineate their physiological and biochemical characteristics. Profiles of thaumarchaeotal and the total archaeal community in the northern South China Sea surface sediments revealed a successively transitional pattern of Thaumarchaeota composition using MiSeq sequencing. Shallow-sea sediment enriched phylotypes decreased gradually along the slope from estuarine and coastal marine region to the deep-sea, while deep-sea sediment enriched phylotypes showed a trend of increasing. Proportion of Thaumarchaeota within the total archaea increased with seawater depth. Phylotypes enriched in shallow- and deep-sea sediments were affiliated to OTUs originated from similar niches, suggesting that physiological adaption not geographical distance shaped the distribution of Thaumarchaeota lineages. Quantitative PCR also depicted a successive decrease of thaumarchaeotal 16S rRNA gene abundance from the highest at shallow-sea sites E708S and E709S (2.57 × 10 6 and 2.73 × 10 6  gene copies/g of dry sediment) to the lowest at deep-sea sites E525S and E407S (1.97 × 10 6 and 2.14 × 10 6  gene copies/g of dry sediment). Both of the abundance fractions of Bathyarchaeota subgroups (including subgroups 1, 6, 8, 10, 13, 15, 17, and ungrouped Bathyarchaeota) and the total Bathyarchaeota in the total archaea showed a negative distribution to seawater depth. Partitioned distribution of Bathyarchaeota fraction in the total archaea is documented for the first time in this study, and the shallow- and deep-sea Bathyarchaeota could account for 17.8 and 0.8%, respectively, on average. Subgroups 6 and 8, enriched subgroups in shallow-sea sediments, largely explained this partitioned distribution pattern according to seawater depth. Their prevalence in shallow-sea and suboxic estuarine sediments rather than deep-sea sediments hints that their metabolic properties of carbon metabolism are adapted to carbon substrates in these environments.

Diversity of Total Bacterial Communities and Chemoautotrophic Populations in Sulfur-Rich Sediments of Shallow-Water Hydrothermal Vents off Kueishan Island, Taiwan.

PubMed

Wang, Li; Cheung, Man Kit; Liu, Rulong; Wong, Chong Kim; Kwan, Hoi Shan; Hwang, Jiang-Shiou

2017-04-01

Shallow-water hydrothermal vents (HTVs) are an ecologically important habitat with a geographic origin similar to that of deep-sea HTVs. Studies on shallow-water HTVs have not only facilitated understanding of the influences of vents on local ecosystems but also helped to extend the knowledge on deep-sea vents. In this study, the diversity of bacterial communities in the sediments of shallow-water HTVs off Kueishan Island, Taiwan, was investigated by examining the 16S ribosomal RNA gene as well as key functional genes involved in chemoautotrophic carbon fixation (aclB, cbbL and cbbM). In the vent area, Sulfurovum and Sulfurimonas of Epsilonproteobacteria appeared to dominate the benthic bacterial community. Results of aclB gene analysis also suggested involvement of these bacteria in carbon fixation using the reductive tricarboxylic acid (rTCA) cycle. Analysis of the cbbM gene showed that Alphaproteobacterial members such as the purple non-sulfur bacteria were the major chemoautotrophic bacteria involving in carbon fixation via the Calvin-Benson-Bassham (CBB) cycle. However, they only accounted for <2% of the total bacterial community in the vent area. These findings suggest that the rTCA cycle is the major chemoautotrophic carbon fixation pathway in sediments of the shallow-water HTVs off Kueishan Island.

77 FR 40073 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... exposed T cells. Methods for generating better T cells to utilize for infusion into patients in adoptive... treated with total body radiation and then receives an infusion of the treated cell culture bone marrow...

Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells.

PubMed

Timocin, Taygun; Ila, Hasan B

2015-01-01

This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs. Genotoxic effect of flurbiprofen was investigated using in vivo chromosome aberration (CA) test and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) test. Also, oxidative stress potential of flurbiprofen was determined by measuring total oxidant and antioxidant level which occurred with flurbiprofen treatment in rat peripheral blood. For these purposes, rats were treated with three concentrations of flurbiprofen (29.25, 58.50 and 117 mg/kg, body weight) in single dose at two different treatment periods (12 and 24 h). According to the results, flurbiprofen did not affect chromosome aberrations in rat bone marrow cells with CA test. In RAPD-PCR test, polymorphic bands were unaffected. Also, test substance did not change total oxidant and antioxidant status (except for 58.50 and 117 mg/kg, 12 h) and therefore it did not lead to significant increase on oxidative stress (again except 58.50 and 117 mg/kg, 12 h). However, flurbiprofen reduced to mitotic indexes and these reductions were dose-dependent for 12 h treatment. In summary, flurbiprofen did not show significant genotoxic effect. But it caused cytotoxicity in rat bone marrow cells.

In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil

PubMed Central

Coronado-Cerda, Erika Evangelina; Franco-Molina, Moisés Armides; Mendoza-Gamboa, Edgar; Prado-García, Heriberto; Rivera-Morales, Lydia Guadalupe; Zapata-Benavides, Pablo; Rodríguez-Salazar, María del Carmen; Caballero-Hernandez, Diana; Tamez-Guerra, Reyes Silvestre; Rodríguez-Padilla, Cristina

2016-01-01

Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable leukocyte extract (bDLE) or IMMUNEPOTENT CRP® (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients. PMID:27191003

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

PubMed Central

Gonzaga, Vivian Fonseca; Lisboa, Gustavo Sabino; Frare, Eduardo Osório

2017-01-01

Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA. PMID:29333168

The Effect of Different Bone Marrow Stimulation Techniques on Human Talar Subchondral Bone: A Micro-Computed Tomography Evaluation.

PubMed

Gianakos, Arianna L; Yasui, Youichi; Fraser, Ethan J; Ross, Keir A; Prado, Marcelo P; Fortier, Lisa A; Kennedy, John G

2016-10-01

To evaluate morphological alterations, microarchitectural disturbances, and the extent of bone marrow access to the subchondral bone marrow compartment using micro-computed tomography analysis in different bone marrow stimulation (BMS) techniques. Nine zones in a 3 × 3 grid pattern were assigned to 5 cadaveric talar dome articular surfaces. A 1.00-mm microfracture awl (s.MFX), a 2.00-mm standard microfracture awl (l.MFX), or a 1.25-mm Kirschner wire (K-wire) drill hole was used to penetrate the subchondral bone in each grid zone. Subchondral bone holes and adjacent tissue areas were assessed by micro-computed tomography to analyze adjacent bone area destruction and communicating channels to the bone marrow. Grades 1 to 3 were assigned, where 1 = minimal compression/sclerosis; 2 = moderate compression/sclerosis; 3 = severe compression/sclerosis. Bone volume/total tissue volume, bone surface area/bone volume, trabecular thickness, and trabecular number were calculated in the region of interest. Visual assessment revealed that the s.MFX had significantly more grade 1 holes (P < .001) and that the l.MFX had significantly more poor/grade 3 holes (P = .002). Bone marrow channel assessment showed a statistically significant increase in the number of channels in the s.MFX when compared with both K-wire and l.MFX holes (P < .001). Bone volume fraction for the s.MFX was significantly less than that of the l.MFX (P = .029). BMS techniques using instruments with larger diameters resulted in increased trabecular compaction and sclerosis in areas adjacent to the defect. K-wire and l.MFX techniques resulted in less open communicating bone marrow channels, denoting a reduction in bone marrow access. The results of this study indicate that BMS using larger diameter devices results in greater microarchitecture disturbances. The current study suggests that the choice of a BMS technique should be carefully considered as the results indicate that smaller diameter hole sizes may diminish the amount of microarchitectural disturbances in the subchondral bone. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Susceptibility and triggering scenarios at a regional scale for shallow landslides

NASA Astrophysics Data System (ADS)

Gullà, G.; Antronico, L.; Iaquinta, P.; Terranova, O.

2008-07-01

The work aims at identifying susceptible areas and pluviometric triggering scenarios at a regional scale in Calabria (Italy), with reference to shallow landsliding events. The proposed methodology follows a statistical approach and uses a database linked to a GIS that has been created to support the various steps of spatial data management and manipulation. The shallow landslide predisposing factors taken into account are derived from (i) the 40-m digital terrain model of the region, an ˜ 15,075 km 2 extension; (ii) outcropping lithology; (iii) soils; and (iv) land use. More precisely, a map of the slopes has been drawn from the digital terrain model. Two kinds of covers [prevalently coarse-grained (CG cover) or fine-grained (FG cover)] were identified, referring to the geotechnical characteristics of geomaterial covers and to the lithology map; soilscapes were drawn from soil maps; and finally, the land use map was employed without any prior processing. Subsequently, the inventory maps of some shallow landsliding events, totaling more than 30,000 instabilities of the past and detected by field surveys and photo aerial restitution, were employed to calibrate the relative importance of these predisposing factors. The use of single factors (first level analysis) therefore provides three different susceptibility maps. Second level analysis, however, enables better location of areas susceptible to shallow landsliding events by crossing the single susceptibility maps. On the basis of the susceptibility map obtained by the second level analysis, five different classes of susceptibility to shallow landsliding events have been outlined over the regional territory: 8.9% of the regional territory shows very high susceptibility, 14.3% high susceptibility, 15% moderate susceptibility, 3.6% low susceptibility, and finally, about 58% very low susceptibility. Finally, the maps of two significant shallow landsliding events of the past and their related rainfalls have been utilized to identify the relevant pluviometric triggering scenarios. By using 205 daily rainfall series, different triggering pluviometric scenarios have been identified with reference to CG and FG covers: a value of 365 mm of the total rainfall of the event and/or 170 mm/d of the rainfall maximum intensity and a value of 325 mm of the total rainfall of the event and/or 158 mm/d of the rainfall maximum intensity are able to trigger shallow landsliding events for CG and FG covers, respectively. The results obtained from this study can help administrative authorities to plan future development activities and mitigation measures in shallow landslide-prone areas. In addition, the proposed methodology can be useful in managing emergency situations at a regional scale for shallow landsliding events triggered by intense rainfalls; through this approach, the susceptibility and the pluviometric triggering scenario maps will be improved by means of finer calibration of the involved factors.

Evidence for organ-specific stem cell microenvironments.

PubMed

Ghinassi, Barbara; Martelli, Fabrizio; Verrucci, Maria; D'Amore, Emanuela; Migliaccio, Giovanni; Vannucchi, Alessandro Maria; Hoffman, Ronald; Migliaccio, Anna Rita

2010-05-01

The X-linked Gata1(low) mutation in mice induces strain-restricted myeloproliferative disorders characterized by extramedullary hematopoiesis in spleen (CD1 and DBA/2) and liver (CD1 only). To assess the role of the microenvironment in establishing this myeloproliferative trait, progenitor cell compartments of spleen and marrow from wild-type and Gata1(low) mice were compared. Phenotype and clonal assay of non-fractionated cells indicated that Gata1(low) mice contain progenitor cell numbers 4-fold lower and 10-fold higher than normal in marrow and spleen, respectively. However, progenitor cells prospectively isolated from spleen, but not from marrow, of Gata1(low) mice expressed colony-forming function in vitro. Therefore, calculation of cloning activity of purified cells demonstrated that the total number of Gata1(low) progenitor cells was 10- to 100-fold lower than normal in marrow and >1,000 times higher than normal in spleen. This observation indicates that Gata1(low) hematopoiesis is favored by the spleen and is in agreement with our previous report that removal of this organ induces wild-type hematopoiesis in heterozygous Gata1(low/+) females (Migliaccio et al., 2009, Blood 114:2107). To clarify if rescue of wild-type hematopoiesis by splenectomy prevented extramedullary hematopoiesis in liver, marrow cytokine expression profile and liver histopathology of splenectomized Gata1(low/+) females were investigated. After splenectomy, the marrow expression levels of TGF-beta, VEGF, osteocalcin, PDGF-alpha, and SDF-1 remained abnormally high while Gata1(low) hematopoiesis was detectable in liver of both CD1 and DBA/2 mutants. Therefore, in the absence of the spleen, Gata1(low) hematopoiesis is supported by the liver suggesting that treatment of myelofibrosis in these animals requires the rescue of both stem cell and microenvironmental functions.

Evidence of bone marrow downregulation in brain-dead rats.

PubMed

Menegat, Laura; Simas, Rafael; Caliman, Julia M; Zanoni, Fernando L; Jacysyn, Jacqueline F; da Silva, Luiz Fernando F; Borelli, Primavera; Moreira, Luiz Felipe P; Sannomiya, Paulina

2017-06-01

Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta 2 -integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Magnetic Resonance Spectroscopy for Evaluating the Effect of Pulsed Electromagnetic Fields on Marrow Adiposity in Postmenopausal Women With Osteopenia.

PubMed

Li, Shaojun; Jiang, Hongning; Wang, Bo; Gu, Mingjun; Bi, Xia; Yin, Ying; Wang, Yu

2018-06-12

Pulsed electromagnetic fields (PEMFs) could promote osteogenic differentiation and suppress adipogenic differentiation in bone mesenchymal stem cells ex vivo. However, data on the effect of PEMF on marrow adiposity in humans remain elusive. We aimed to determine the in vivo effect of PEMF on marrow adiposity in postmenopausal women using magnetic resonance spectroscopy. Sixty-one postmenopausal women with osteopenia, aged 53 to 85 years, were randomly assigned to receive either PEMF treatment or placebo. The session was performed 3 times per week for 6 months. All women received adequate dietary calcium and vitamin D. Bone mineral density (BMD) by dual-energy x-ray absorptiometry, vertebral marrow fat content by magnetic resonance spectroscopy, and serum biomarkers were evaluated before and after 6 months of treatment. A total of 27 (87.1%) and 25 (83.3%) women completed the treatment schedule in the PEMF and placebo groups, respectively. After the 6-month treatment, lumbar spine and hip BMD increased by 1.46% to 2.04%, serum bone-specific alkaline phosphatase increased by 3.23%, and C-terminal telopeptides of type 1 collagen decreased by 9.12% in the PEMF group (P < 0.05), whereas the mean percentage changes in BMD and serum biomarkers were not significant in the placebo group. Pulsed electromagnetic field treatment significantly reduced marrow fat fraction by 4.81%. The treatment difference between the 2 groups was -4.43% (95% confidence interval, -3.70% to -5.65%; P = 0.009). Pulsed electromagnetic field is an effective physiotherapy in postmenopausal women, and this effect may, at least in part, regulate the amount of fat within the bone marrow. Magnetic resonance spectroscopy may serve as a complementary imaging biomarker for monitoring response to therapy in osteoporosis.

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

PubMed Central

Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

PubMed

Govey, Peter M; Zhang, Yue; Donahue, Henry J

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

[Bone marrow transplantation in aplastic anemia. Experience at a Mexican institution. Bone marrow transplantation group of the Salvador Zubirán National Institute of Nutrition].

PubMed

León-Rodríguez, E; Sosa Sánchez, R; Gómez, E; Ochoa Sosa, C

1993-01-01

During the period of May 1986 through February 1991, nine allogeneic bone marrow transplants (BMT) on eight severe aplastic anemia (SAA) patients were performed at the Instituto Nacional de la Nutrición Salvador Zubirán in Mexico City. Mean age at BMT was 18 years (age interval 12-30); seven were men; all patients had a clinical history of multiple blood transfusions; six individuals were infected at the time of the transplant. The conditioning regimens were: cyclophosphamide (Cy) in three patients; Cy+ total nodal radiation in five; and total nodal radiation only in the second transplant of one patient. Graft versus host disease (GVHD) prophylaxis was attempted with methotrexate plus cyclosporin A (CsA) in six patients, methylprednisolone plus CsA in two, and prednisone + CsA in the patient retransplanted. All procedures were carried out under single reverse isolation without gut decontamination. Seven of the nine procedures grafted (two cases died on days +8 and +25 due to infection). In the surviving, the median time for reaching > 1.0 white blood cells x 10(9)/L was 22 days (time interval 11-31); > 0.5 neutrophils x 10(9)/L in 27 days (time interval 15-42) and the same lapse to reach > 50 platelets x 10(9)/L. Length of hospital stay was 42 days (time interval 15-61). Acute GVHD was seen in one of the seven patients surviving the period of bone marrow aplasia (14%). Of six long term survivors (including one patient with a second transplant) chronic GVHD was present in four (67%): chronic GVHD was fatal in one individual but was well controlled in three.(ABSTRACT TRUNCATED AT 250 WORDS)

Dosimetric evaluation of total marrow irradiation using 2 different planning systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nalichowski, Adrian, E-mail: nalichoa@karmanos.org; Eagle, Don G.; Burmeister, Jay

This study compared 2 different treatment planning systems (TPSs) for quality and efficiency of total marrow irradiation (TMI) plans. The TPSs used in this study were VOxel-Less Optimization (VoLO) (Accuray Inc, Sunnyvale, CA) using helical dose delivery on a Tomotherapy Hi-Art treatment unit and Eclipse (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) dose delivery on a Varian iX treatment unit. A total dose of 1200 cGy was prescribed to cover 95% of the planning target volume (PTV). The plans were optimized and calculated based on a single CT data and structure set using themore » Alderson Rando phantom (The Phantom Laboratory, Salem, NY) and physician contoured target and organ at risk (OAR) volumes. The OARs were lungs, heart, liver, kidneys, brain, and small bowel. The plans were evaluated based on plan quality, time to optimize the plan and calculate the dose, and beam on time. The resulting mean and maximum doses to the PTV were 1268 and 1465 cGy for VoLO and 1284 and 1541 cGy for Eclipse, respectively. For 5 of 6 OAR structures the VoLO system achieved lower mean and D10 doses ranging from 22% to 52% and 3% to 44%, respectively. Total computational time including only optimization and dose calculation were 0.9 hours for VoLO and 3.8 hours for Eclipse. These times do not include user-dependent target delineation and field setup. Both planning systems are capable of creating high-quality plans for total marrow irradiation. The VoLO planning system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing. VoLO's graphics processing unit (GPU)–based optimization and dose calculation algorithm also allowed much faster creation of TMI plans.« less

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

PubMed

Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

1988-02-01

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to the limitations of the theoretical analysis.

Resection and Resolution of Bone Marrow Lesions Associated with an Improvement of Pain after Total Knee Replacement: A Novel Case Study Using a 3-Tesla Metal Artefact Reduction MRI Sequence.

PubMed

Kurien, Thomas; Kerslake, Robert; Haywood, Brett; Pearson, Richard G; Scammell, Brigitte E

2016-01-01

We present our case report using a novel metal artefact reduction magnetic resonance imaging (MRI) sequence to observe resolution of subchondral bone marrow lesions (BMLs), which are strongly associated with pain, in a patient after total knee replacement surgery. Large BMLs were seen preoperatively on the 3-Tesla MRI scans in a patient with severe end stage OA awaiting total knee replacement surgery. Twelve months after surgery, using a novel metal artefact reduction MRI sequence, we were able to visualize the bone-prosthesis interface and found complete resection and resolution of these BMLs. This is the first reported study in the UK to use this metal artefact reduction MRI sequence at 3-Tesla showing that resection and resolution of BMLs in this patient were associated with an improvement of pain and function after total knee replacement surgery. In this case it was associated with a clinically significant improvement of pain and function after surgery. Failure to eradicate these lesions may be a cause of persistent postoperative pain that is seen in up to 20% of patients following TKR surgery.

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging

PubMed Central

Tuljapurkar, Sonal R; McGuire, Timothy R; Brusnahan, Susan K; Jackson, John D; Garvin, Kevin L; Kessinger, Margaret A; Lane, Judy T; O' Kane, Barbara J; Sharp, John G

2011-01-01

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells. PMID:21923862

The Effect of Classical Turkish Music on Pain Severity and Anxiety Levels in Patients Undergoing Bone Marrow Aspiration and Biopsy.

PubMed

Özdemir, Ülkü; Taşcı, Sultan; Yıldızhan, Esra; Aslan, Süheyla; Eser, Bülent

2018-05-18

Bone marrow aspiration is a painful procedure. In addition, the anxiety experienced during the procedure can affect the pain felt during the procedure. This study was conducted as a randomized controlled study to determine the effect of classical Turkish music on pain severity and anxiety levels in patients undergoing bone marrow aspiration and biopsy. The study was performed in an oncology hospital with a total of 30 patients, of whom 14 were in the intervention group and 16 were in the control group. All underwent bone marrow aspiration and biopsy for the first time. Ethics committee approval, institutional permission, and the study participants' written informed consent were obtained. Data were collected using patient information forms and follow-up charts, the Visual Analog Scale, and the State Anxiety Inventory. It was determined that the scores gathered from the State Anxiety Inventory during the first follow-up increased in the second follow-up in both the intervention and control groups, and this increase was statistically significant in the intervention group (p < .05). The mean pain severity scores of the patients undergoing the procedure were significantly lower in the intervention group than in the control group (p < .05). This study found that classical Turkish music reduced the severity of pain but increased the levels of anxiety in patients undergoing bone marrow aspiration and biopsy. Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis.

PubMed

Hussein, K; Stucki-Koch, A; Göhring, G; Kreipe, H; Suttorp, M

2017-07-01

Paediatric chronic myeloid leukaemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for paediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients, but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix-modulating factors shifts the bone marrow microenvironment towards fibrosis.

Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical cancer.

PubMed

Yan, Kevin; Ramirez, Ezequiel; Xie, Xian-Jin; Gu, Xuejun; Xi, Yin; Albuquerque, Kevin

The purpose of this study was to determine factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node metastasis treated with concurrent cisplatin chemoradiation to an extended field (EFCRT). Thirty-eight patients with cervical cancer and para-aortic lymph node metastasis who underwent EFCRT were analyzed. Active bone marrow was defined as the region within irradiated total bone marrow (BM TOT ) with a standard uptake value on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography greater than the mean standard uptake value for BM TOT . Serial weekly blood counts from the beginning to the end of radiation treatment were evaluated for HT using Common Terminology Criteria for Adverse Events, version 4.0. Nineteen patients had grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Obese patients (n = 12) were less likely to get HT3+ (P = .03) despite getting equivalent doses of chemotherapy. Volumes of BM TOT and active bone marrow receiving doses of 20, 30, and 45 Gy and body mass index significantly predicted HT3+. Patients who had HT3+ had prolonged treatment time (62 vs 53 days, P < .001). For patients receiving EFCRT, bone marrow irradiation parameters and patient body mass index were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients, allowing the potential to explore bone marrow-sparing delivery techniques. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

The Total-Pressure Recovery and Drag Characteristics of Several Auxiliary Inlets at Transonic Speeds

NASA Technical Reports Server (NTRS)

Dennard, John S.

1959-01-01

Several flush and scoop-type auxiliary inlets have been tested for a range of Mach numbers from 0.55 to 1.3 to determine their transonic total-pressure recovery and drag characteristics. The inlet dimensions were comparable with the thickness of the boundary layer in which they were tested. Results indicate that flush inlets should be inclined at very shallow angles with respect to the surface for optimum total-pressure recovery and drag characteristics. Deep, narrow inlets have lower drag than wide shallow ones at Mach numbers greater than 0.9 but at lower Mach numbers the wider inlets proved superior. Inlets with a shallow approach ramp, 7 deg, and diverging ramp walls which incorporated boundary-layer bypass had lower drag than any other inlet tested for Mach numbers up to 1.2 and had the highest pressure recovery of all of the flush inlets. The scoop inlets, which operated in a higher velocity flow than the flush inlets, had higher drag coefficients. Several of these auxiliary inlets projected multiple, periodic shock waves into the stream when they were operated at low mass-flow ratios.

Successful pregnancy following very high-dose total body irradiation (1575 cGy) and bone marrow transplantation in a woman with acute myeloid leukemia.

PubMed

Wang, W S; Tzeng, C H; Hsieh, R K; Chiou, T J; Liu, J H; Yen, C C; Chen, P M

1998-02-01

A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy x 7, at a dose rate of 3.5 cGy/min). Graft-versus-host disease prophylaxis was with methotrexate and cyclosporin A. Grade I acute GVHD developed after BMT but there was no chronic GVHD. She became amenorrhoeic after BMT and serial gonadal testing indicated hypergonadotrophic hypogonadism. She became pregnant and delivered a full-term, healthy baby 6 years after BMT. Successful pregnancy after TBI of more than 1200 cGy is extremely rare. This case, to the best of our knowledge, is the second patient who received a higher dose of TBI (1575 cGy) to have a successful pregnancy. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 1200 cGy.

Community structure of age-0 fishes in paired mainstem and created shallow-water habitats in the Lower Missouri River

USGS Publications Warehouse

Starks, Trevor A.; Long, James M.; Dzialowski, Andrew R.

2016-01-01

Anthropogenic alterations to aquatic ecosystems have greatly reduced and homogenized riverine habitat, especially those used by larval and juvenile fishes. Creation of shallow-water habitats is used as a restoration technique in response to altered conditions in several studies globally, but only recently in the USA. In the summer of 2012, the U.S. Army Corps of Engineers sampled larval and juvenile fishes at six paired sites (mainstem and constructed chute shallow-water habitats) along a section of the Missouri River between Rulo, NE and St. Louis, MO, USA. From those samples, we enumerated and identified a total of 7622 fishes representing 12 families. Community responses of fishes to created shallow-water habitats were assessed by comparisons of species richness and diversity measures between paired sites and among sampling events. Shannon entropy measures were transformed, and gamma diversity (total diversity) was partitioned into two components, alpha (within community) and beta (between community) diversity using a multiplicative decomposition method. Mantel test results suggest site location, time of sampling event and habitat type were drivers of larval and juvenile community structure. Paired t-test results indicated little to no differences in beta diversity between habitat types; however, chute habitats had significantly higher alpha and gamma diversity as well as increased abundances of Asian carp larvae when compared with mainstem shallow-water habitat. Our results not only show the importance of created shallow-water habitat in promoting stream fish diversity but also highlight the role space and time may play in future restoration and management efforts. 

An image-based skeletal tissue model for the ICRP reference newborn

NASA Astrophysics Data System (ADS)

Pafundi, Deanna; Lee, Choonsik; Watchman, Christopher; Bourke, Vincent; Aris, John; Shagina, Natalia; Harrison, John; Fell, Tim; Bolch, Wesley

2009-07-01

Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set—both male and female—that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in mineral bone composition may have significant dosimetric implications when considering localized marrow dosimetry for radionuclides that target mineral bone in the newborn child.

Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy

PubMed Central

Whitney, Daniel G.; Singh, Harshvardhan; Miller, Freeman; Barbe, Mary F.; Slade, Jill M.; Pohlig, Ryan T.; Modlesky, Christopher M.

2016-01-01

Introduction Nonambulatory children with severe cerebral palsy (CP) have an underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. Materials and methods Ambulatory children with mild spastic CP and typically developing children (4 to 11 years; 12/group) were tested. Magnetic resonance imaging was used to estimate cortical, medullary and total bone volume and width, bone strength [i.e., section modulus (Z) and polar moment of inertia (J)], and bone marrow fat concentration in the midtibia, and muscle volume, intermuscular, subfascial, and subcutaneous adipose tissue (AT) volume and intramuscular fat concentration in the midleg. Physical activity monitors worn on the ankle were used to assess physical activity. Results There were no group differences in age, height, body mass, body mass percentile, BMI, BMI percentile or tibia length, but children with CP had lower height percentile (19th vs. 50th percentile) and total physical activity counts (44 %) than controls (both p < 0.05). Children with CP also had lower cortical volume (30 %), cortical width in the posterior (16 %) and medial (32 %) portion of the shaft, total bone width in the medial-lateral direction (15 %), Z in the medial-lateral direction (34 %), J (39 %) and muscle volume (39 %), and higher bone marrow fat concentration (82.1 ± 1.8 % vs. 80.5 ± 1.9 %), subfascial AT volume (3.3 fold) and intramuscular fat concentration (25.0 ± 8.0 % vs. 16.1 ± 3.3 %) than controls (all p < 0.05). When tibia length was statistically controlled, all group differences in bone architecture, bone strength, muscle volume and fat infiltration estimates, except posterior cortical width, were still present (all p < 0.05). Furthermore, a higher intermuscular AT volume in children with CP compared to controls emerged (p < 0.05). Conclusions Ambulatory children with mild CP exhibit an underdeveloped bone architecture and low bone strength in the midtibia and a greater infiltration of fat in the bone marrow and surrounding musculature compared to typically developing children. Whether the deficit in the musculoskeletal system of children with CP is associated with higher chronic disease risk and whether the deficit can be mitigated requires further investigation. PMID:27732905

Growth in children following irradiation for bone marrow transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bushhouse, S.; Ramsay, N.K.; Pescovitz, O.H.

Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant lossmore » in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression.« less

Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1-, IL-17-, and G-CSF-dependent manner.

PubMed

Capitano, Maegan L; Nemeth, Michael J; Mace, Thomas A; Salisbury-Ruf, Christi; Segal, Brahm H; McCarthy, Philip L; Repasky, Elizabeth A

2012-09-27

Neutropenia is a common side effect of cytotoxic chemotherapy and radiation, increasing the risk of infection in these patients. Here we examined the impact of body temperature on neutrophil recovery in the blood and bone marrow after total body irradiation (TBI). Mice were exposed to either 3 or 6 Gy TBI followed by a mild heat treatment that temporarily raised core body temperature to approximately 39.5°C. Neutrophil recovery was then compared with control mice that received either TBI alone heat treatment alone. Mice that received both TBI and heat treatment exhibited a significant increase in the rate of neutrophil recovery in the blood and an increase in the number of marrow hematopoietic stem cells and neutrophil progenitors compared with that seen in mice that received either TBI or heat alone. The combination treatment also increased G-CSF concentrations in the serum, bone marrow, and intestinal tissue and IL-17, IL-1β, and IL-1α concentrations in the intestinal tissue after TBI. Neutralizing G-CSF or inhibiting IL-17 or IL-1 signaling significantly blocked the thermally mediated increase in neutrophil numbers. These findings suggest that a physiologically relevant increase in body temperature can accelerate recovery from neutropenia after TBI through a G-CSF-, IL-17-, and IL-1-dependent mechanism.

Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1–, IL-17–, and G-CSF–dependent manner

PubMed Central

Capitano, Maegan L.; Nemeth, Michael J.; Mace, Thomas A.; Salisbury-Ruf, Christi; Segal, Brahm H.; McCarthy, Philip L.

2012-01-01

Neutropenia is a common side effect of cytotoxic chemotherapy and radiation, increasing the risk of infection in these patients. Here we examined the impact of body temperature on neutrophil recovery in the blood and bone marrow after total body irradiation (TBI). Mice were exposed to either 3 or 6 Gy TBI followed by a mild heat treatment that temporarily raised core body temperature to approximately 39.5°C. Neutrophil recovery was then compared with control mice that received either TBI alone heat treatment alone. Mice that received both TBI and heat treatment exhibited a significant increase in the rate of neutrophil recovery in the blood and an increase in the number of marrow hematopoietic stem cells and neutrophil progenitors compared with that seen in mice that received either TBI or heat alone. The combination treatment also increased G-CSF concentrations in the serum, bone marrow, and intestinal tissue and IL-17, IL-1β, and IL-1α concentrations in the intestinal tissue after TBI. Neutralizing G-CSF or inhibiting IL-17 or IL-1 signaling significantly blocked the thermally mediated increase in neutrophil numbers. These findings suggest that a physiologically relevant increase in body temperature can accelerate recovery from neutropenia after TBI through a G-CSF–, IL-17–, and IL-1–dependent mechanism. PMID:22806894

Probabilistic evaluation of shallow groundwater resources at a hypothetical carbon sequestration site

DOE PAGES

Dai, Zhenxue; Keating, Elizabeth; Bacon, Diana H.; ...

2014-03-07

Carbon sequestration in geologic reservoirs is an important approach for mitigating greenhouse gases emissions to the atmosphere. This study first develops an integrated Monte Carlo method for simulating CO 2 and brine leakage from carbon sequestration and subsequent geochemical interactions in shallow aquifers. Then, we estimate probability distributions of five risk proxies related to the likelihood and volume of changes in pH, total dissolved solids, and trace concentrations of lead, arsenic, and cadmium for two possible consequence thresholds. The results indicate that shallow groundwater resources may degrade locally around leakage points by reduced pH and increased total dissolved solids (TDS).more » The volumes of pH and TDS plumes are most sensitive to aquifer porosity, permeability, and CO 2 and brine leakage rates. The estimated plume size of pH change is the largest, while that of cadmium is the smallest among the risk proxies. Plume volume distributions of arsenic and lead are similar to those of TDS. The scientific results from this study provide substantial insight for understanding risks of deep fluids leaking into shallow aquifers, determining the area of review, and designing monitoring networks at carbon sequestration sites.« less

Bone Marrow Stem Cells Added to a Hydroxyapatite Scaffold Result in Better Outcomes after Surgical Treatment of Intertrochanteric Hip Fractures

PubMed Central

Gutierres, Manuel; Lopes, M. Ascenção; Santos, J. Domingos; Cabral, A. T.; Pinto, R.

2014-01-01

Introduction. Intertrochanteric hip fractures occur in the proximal femur. They are very common in the elderly and are responsible for high rates of morbidity and mortality. The authors hypothesized that adding an autologous bone marrow stem cells concentrate (ABMC) to a hydroxyapatite scaffold and placing it in the fracture site would improve the outcome after surgical fixation of intertrochanteric hip fractures. Material and Methods. 30 patients were randomly selected and divided into 2 groups of 15 patients, to receive either the scaffold enriched with the ABMC (Group A) during the surgical procedure, or fracture fixation alone (Group B). Results. There was a statistically significant difference in favor of group A at days 30, 60, and 90 for Harris Hip Scores (HHS), at days 30 and 60 for VAS pain scales, for bedridden period and time taken to start partial and total weight bearing (P < 0.05). Discussion. These results show a significant benefit of adding a bone marrow enriched scaffold to surgical fixation in intertrochanteric hip fractures, which can significantly reduce the associated morbidity and mortality rates. Conclusion. Bone marrow stem cells added to a hydroxyapatite scaffold result in better outcomes after surgical treatment of intertrochanteric hip fractures. PMID:24955356

Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

PubMed Central

Cesar, Beatriz; Abud, Ana Paula R.; de Oliveira, Carolina C.; Cardoso, Francolino; Bernardi, Raffaello Popa Di; Guimarães, Fernando S. F.; Gabardo, Juarez; de Freitas Buchi, Dorly

2011-01-01

A homeopathic complex medication (HCM), with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now report in vivo immunophenotyping of total bone marrow cells and ex vivo effects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measured in vitro. After in vivo treatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects of ex vivo HCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were induced in vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products. PMID:19736221

High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors

ClinicalTrials.gov

2013-05-07

Breast Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Bone Marrow Aspirate Concentrate for Cartilage Defects of the Knee: From Bench to Bedside Evidence.

PubMed

Cotter, Eric J; Wang, Kevin C; Yanke, Adam B; Chubinskaya, Susan

2018-04-01

Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including ["bone marrow aspirate" and "cartilage"], ["mesenchymal stem cells" and "cartilage"], and ["bone marrow aspirate" and "mesenchymal stem cells" and "orthopedics"]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived-mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.

Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice.

PubMed

Farace, Francoise; Prestoz, Laetitita; Badaoui, Sabrina; Guillier, Martine; Haond, Celine; Opolon, Paule; Thomas, Jean-Leon; Zalc, Bernard; Vainchenker, William; Turhan, Ali G

2004-02-01

Muscle tissue of adult mice has been shown to contain stem cells with hematopoietic repopulation ability in vivo. To determine the functional characteristics of stem cells giving rise to this hematopoietic activity, we have performed hematopoietic reconstitution experiments by the use of muscle versus marrow transplantation in lethally irradiated mice and followed the fate of transplanted cells by Y-chimerism using PCR and fluorescence in situ hybridization (FISH) analysis. We report here that transplantation of murine muscle generate a major hematopoietic chimerism at the level of CFU-C, CFU-S, and terminally-differentiated cells in three generations of lethally irradiated mice followed up to 1 year after transplantation. This potential is totally abolished when muscle grafts were performed by the use of muscle from previously irradiated mice. As compared to marrow transplantation, muscle transplants were able to generate similar potencies to give rise to myeloid, T, B, and natural killer (NK) cells. Interestingly, marrow stem cells that have been generated in primary and then in secondary recipients were able to contribute efficiently to myofibers in the muscle tissue of tertiary recipients. Altogether, our data demonstrate that muscle-derived stem cells present a major hematopoietic repopulating ability with evidence of self-replication in vivo. They are radiation-sensitive and similar to marrow-derived stem cells in terms of their ability to generate multilineage hematopoiesis. Finally, our data demonstrate that muscle-derived hematopoietic stem cells do not lose their ability to contribute to myofiber generation after at least two rounds of serial transplantation, suggesting a potential that is probably equivalent to that generated by marrow transplantation.

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging.

PubMed

Tuljapurkar, Sonal R; McGuire, Timothy R; Brusnahan, Susan K; Jackson, John D; Garvin, Kevin L; Kessinger, Margaret A; Lane, Judy T; O' Kane, Barbara J; Sharp, John G

2011-11-01

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Immunophenotyping in systemic mastocytosis diagnosis: 'CD25 positive' alone is more informative than the 'CD25 and/or CD2' WHO criterion.

PubMed

Morgado, José Mário T; Sánchez-Muñoz, Laura; Teodósio, Cristina G; Jara-Acevedo, Maria; Alvarez-Twose, Iván; Matito, Almudena; Fernández-Nuñez, Elisa; García-Montero, Andrés; Orfao, Alberto; Escribano, Luís

2012-04-01

Aberrant expression of CD2 and/or CD25 by bone marrow, peripheral blood or other extracutaneous tissue mast cells is currently used as a minor World Health Organization diagnostic criterion for systemic mastocytosis. However, the diagnostic utility of CD2 versus CD25 expression by mast cells has not been prospectively evaluated in a large series of systemic mastocytosis. Here we evaluate the sensitivity and specificity of CD2 versus CD25 expression in the diagnosis of systemic mastocytosis. Mast cells from a total of 886 bone marrow and 153 other non-bone marrow extracutaneous tissue samples were analysed by multiparameter flow cytometry following the guidelines of the Spanish Network on Mastocytosis at two different laboratories. The 'CD25+ and/or CD2+ bone marrow mast cells' World Health Organization criterion showed an overall sensitivity of 100% with 99.0% specificity for the diagnosis of systemic mastocytosis whereas CD25 expression alone presented a similar sensitivity (100%) with a slightly higher specificity (99.2%). Inclusion of CD2 did not improve the sensitivity of the test and it decreased its specificity. In tissues other than bone marrow, the mast cell phenotypic criterion revealed to be less sensitive. In summary, CD2 expression does not contribute to improve the diagnosis of systemic mastocytosis when compared with aberrant CD25 expression alone, which supports the need to update and replace the minor World Health Organization 'CD25+ and/or CD2+' mast cell phenotypic diagnostic criterion by a major criterion based exclusively on CD25 expression.

The troposphere-to-stratosphere transition in kinetic energy spectra and nonlinear spectral fluxes as seen in ECMWF analyses

NASA Astrophysics Data System (ADS)

Burgess, A. B. H.; Erler, A. R.; Shepherd, T. G.

2012-04-01

We present spectra, nonlinear interaction terms, and fluxes computed for horizontal wind fields from high-resolution meteorological analyses made available by ECMWF for the International Polar Year. Total kinetic energy spectra clearly show two spectral regimes: a steep spectrum at large scales and a shallow spectrum in the mesoscale. The spectral shallowing appears at ~200 hPa, and is due to decreasing rotational power with height, which results in the shallower divergent spectrum dominating in the mesoscale. The spectra we find are steeper than those observed in aircraft data and GCM simulations. Though the analyses resolve total spherical harmonic wavenumbers up to n = 721, effects of dissipation on the fluxes and spectra are visible starting at about n = 200. We find a weak forward energy cascade and a downscale enstrophy cascade in the mesoscale. Eddy-eddy nonlinear kinetic energy transfers reach maximum amplitudes at the tropopause, and decrease with height thereafter; zonal mean-eddy transfers dominate in the stratosphere. In addition, zonal anisotropy reaches a minimum at the tropopause. Combined with strong eddy-eddy interactions, this suggests flow in the tropopause region is very active and bears the greatest resemblance to isotropic turbulence. We find constant enstrophy flux over a broad range of wavenumbers around the tropopause and in the upper stratosphere. A relatively constant spectral enstrophy flux at the tropopause suggests a turbulent inertial range, and that the enstrophy flux is resolved. A main result of our work is its implications for explaining the shallow mesoscale spectrum observed in aircraft wind measurements, GCM studies, and now meteorological analyses. The strong divergent component in the shallow mesoscale spectrum indicates unbalanced flow, and nonlinear transfers decreasing quickly with height are characteristic of waves, not turbulence. Together with the downscale flux of energ y through the shallow spectral range, these findings add further evidence that the shallow mesoscale spectrum is not generated by balanced two-dimensional turbulence.

A Novel microCT Method for Bone and Marrow Adipose Tissue Alignment Identifies Key Differences Between Mandible and Tibia in Rats.

PubMed

Coutel, Xavier; Olejnik, Cécile; Marchandise, Pierre; Delattre, Jérôme; Béhal, Hélène; Kerckhofs, Greet; Penel, Guillaume

2018-01-30

Bone homeostasis is influenced by the bone marrow adipose tissue (BMAT). BMAT distribution varies from one anatomical location in the skeleton to another. We developed an advanced microfocus computed tomography imaging and analysis protocol that allows accurate alignment of both the BMAT distribution and bone micro-architecture as well as calculation of the distance of the BMAT adipocytes from the bone surface. Using this protocol, we detected a different spatial BMAT distribution between the rat tibia and mandible: in the proximal metaphysis of the tibia a large amount of BMAT (~ 20% of the total BMAT) was located close to the bone surface (< 20 µm), whereas in the alveolar ridge ~ 30% of the total BMAT was located between 40 and 60 µm from the bone surface. In the alveolar ridge of rats, the trabecular bone volume was 48.3% higher compared to the proximal metaphysis of the tibia (p < 0.0001) and the percentage of adiposity determined to the relative marrow volume was lower (1.5%) compared to the proximal metaphysis of the tibia (9%, p = 0.0002). Interestingly, in the tibia a negative correlation was found between the percentage of adiposity in the total volume and the trabecular thickness (r =- 0.74, p = 0.037). The present study highlights that in comparison to tibial proximal metaphysis, the mandibular bone exhibits a massive trabecular network and a low BMAT content with almost no contact with the bone surface. These findings are of great interest because of the importance of the fat-bone interaction and its potential relevance to several resorptive bone diseases.

Temporal-spatial variations and influencing factors of nitrogen in the shallow groundwater of the nearshore vegetable field of Erhai Lake, China.

PubMed

Chen, Anqiang; Lei, Baokun; Hu, Wanli; Wang, Hongyuan; Zhai, Limei; Mao, Yanting; Fu, Bin; Zhang, Dan

2018-02-01

Nitrogen export from the nearshore vegetable field of Erhai Lake seriously threatens the water quality of Erhai Lake, which is the second largest highland freshwater lake in Yunnan Province, China. Among the nitrogen flows into Erhai Lake, shallow groundwater migration is a major pathway. The nitrogen variation and influencing factors in the shallow groundwater of the nearshore vegetable field of Erhai Lake are not well documented. A 2-year field experiment was conducted to determine the concentrations of nitrogen species in the shallow groundwater and their influencing factors in the nearshore vegetable field of Erhai Lake. The results showed that concentrations of TN, NO 3 - -N, and NO 2 - -N gradually increased with increasing elevation and distance from Erhai Lake, but the opposite was observed for NH 4 + -N in the shallow groundwater. The concentrations of nitrogen species in the rainy season were greater than those in the dry season. NO 3 - -N accounted for more than 79% of total nitrogen in shallow groundwater. Redundancy analysis showed that more than 70% of the temporal and spatial variations of nitrogen concentrations in the shallow groundwater were explained by shallow groundwater depth, and only approximately 10% of variation was explained by the factors of soil porosity, silt clay content of soil, and NH 4 + -N and NO 3 - -N concentrations of soil (p < 0.05). The shallow groundwater depth had more notable effects on nitrogen concentrations in the shallow groundwater than other factors. This result will strongly support the need for further research regarding the management practices for reducing nitrogen concentrations in shallow groundwater.

Assessment of concentrations of trace elements in ground water and soil at the Small-Arms Firing Range, Shaw Air Force Base, South Carolina

USGS Publications Warehouse

Landmeyer, J.E.

1994-01-01

Ground-water samples were collected from four shallow water-table aquifer observation wells beneath the Small-Arms Firing Range study area at Shaw Air Force Base. Water-chemistry analyses indicated that total lead concentrations in shallow ground water beneath the study area do not exceed the U.S. Environmental Protection Agency maximum contaminant level established for lead in drinking water (0.05 milligrams per liter). All other trace element total concentrations in ground water beneath the study area were at or below the detection limit of the analytical methodology.

Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant

ClinicalTrials.gov

2017-07-12

Adenosine Deaminase Deficiency; Autosomal Recessive Disorder; Immune System Disorder; Purine-Nucleoside Phosphorylase Deficiency; Severe Combined Immunodeficiency; Severe Combined Immunodeficiency With Absence of T and B Cells; X-Linked Severe Combined Immunodeficiency

Total Marrow and Lymphoid Irradiation, Fludarabine, and Melphalan Before Donor Stem Cell Transplant in Treating Participants With High-Risk Acute Leukemia or Myelodysplastic Syndrome

ClinicalTrials.gov

2018-06-01

Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Hematopoietic Cell Transplantation Recipient; Minimal Residual Disease; Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia

Donation FAQs

MedlinePlus

... to-six-week period. This does not include travel time, which is defined by air travel and staying overnight in a hotel. Nearly 40% of donors will travel during the donation process. Marrow and PBSC donation require about the same total time commitment. What if I have medical complications related ...

Bone marrow aspiration

MedlinePlus

Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

PubMed

Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong; Kim, Hee Chan

2017-01-01

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method as an automated white blood cell differential count system.

White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks

PubMed Central

Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong

2017-01-01

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method as an automated white blood cell differential count system. PMID:29228051

Water quality in shallow alluvial aquifers, Upper Colorado River Basin, Colorado, 1997

USGS Publications Warehouse

Apodaca, L.E.; Bails, J.B.; Smith, C.M.

2002-01-01

Shallow ground water in areas of increasing urban development within the Upper Colorado River Basin was sampled for inorganic and organic constituents to characterize water-quality conditions and to identify potential anthropogenic effects resulting from development. In 1997, 25 shallow monitoring wells were installed and sampled in five areas of urban development in Eagle, Grand, Gunnison, and Summit Counties, Colorado. The results of this study indicate that the shallow ground water in the study area is suitable for most uses. Nonparametric statistical methods showed that constituents and parameters measured in the shallow wells were often significantly different between the five developing urban areas. Radon concentrations exceeded the proposed USEPA maximum contaminant level at all sites. The presence of nutrients, pesticides, and volatile organic compounds indicate anthropogenic activities are affecting the shallow ground-water quality in the study area. Nitrate as N concentrations greater than 2.0 mg/L were observed in ground water recharged between the 1980s and 1990s. Low concentrations of methylene blue active substances were detected at a few sites. Total coliform bacteria were detected at ten sites; however, E. coli was not detected. Continued monitoring is needed to assess the effects of increasing urban development on the shallow ground-water quality in the study area.

Neutrophilic progression in a case of polycytemia vera mimicking chronic neutrophilic leukemia: clinical and molecular characterization.

PubMed

Castelli, Roberto; Cugno, Massimo; Gianelli, Umberto; Pancrazzi, Alessandro; Vannucchi, Alessandro Maria

2015-04-01

In a small subset of polycytemia vera (PV), neutrophilia not secondary to reactive conditions or treatment can develop and persist. Clinical significance and morphogenetic alterations associated with this uncommon phenomenon are not well defined. An 81-year-old Caucasian woman, affected by polycytemia vera lasting 17 years, presented in March 2012 with hyperleukocytosis, absolute neutrophilia, and thrombocytosis despite hydroxyurea treatment. All other laboratory parameters were normal, except for an increased neutrophil alkaline phosphatase and lactate dehydrogenase. Reactive neutrophilia due to infection or neoplasia have been ruled out by a total body computerized tomography scan, and by low levels of C reactive protein. Re-evaluation of bone marrow showed hypercellular smears with expansion of granulopoiesis while immature granulocytes were <10% and myeloblasts were <1%. Bone marrow trephine biopsy showed hypercellular marrow, with panmyelosis, increased myeloid/erithroid ratio, polymorphic clusters of megakaryocytes. A loose network of reticulin fibers with many intersections was identified by means of Gomori's silver impregnation. There were no hybrid BCR/ABL gene transcripts of p210, p190 and p230, no mutations in platelet derived growth factor receptors alpha and beta. Flow cytometry on the aspirate showed that CD34+ CD117+ myeloblasts constituted less than 1% of total marrow nucleated cells, mature granulocytes demonstrated persistent expression of CD33. Mutational analysis of the gene CSF3R by PCR amplification revealed no alterations in exons 14-17, including codons 615 and 618. The case presented here represents a possible evolution of PV, albeit very rare. The condition described here differs from the CNL for the persistence of morphological pictures typical of myeloproliferative diseases, for absence of CSF3R gene mutations and for the hyper expansion of the mature granulopoietic series. The clinical significance and morphogenetic alterations associated with this uncommon phenomenon are not well defined. Copyright © 2014 Elsevier GmbH. All rights reserved.

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aerts-Kaya, Fatima S.F.; Visser, Trudi P.; Arshad, Shazia

Purpose: 5-Androstene-3{beta},17{beta}-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. Methods and Materials: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. Results: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unitmore » (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. Conclusions: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.« less

The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.

PubMed

Guerrero, Julien; Oliveira, Hugo; Catros, Sylvain; Siadous, Robin; Derkaoui, Sidi-Mohammed; Bareille, Reine; Letourneur, Didier; Amédée, Joëlle

2015-03-01

Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.

The Effects of a Transition to Minimalist Shoe Running on Intrinsic Foot Muscle Size.

PubMed

Johnson, A W; Myrer, J W; Mitchell, U H; Hunter, I; Ridge, S T

2016-02-01

A proposed benefit of minimalist shoe running is an increase in intrinsic foot muscle strength. This study examined change in intrinsic foot muscle size in runners transitioning to Vibram FiveFingers™ minimalist shoes compared to a control group running in traditional running shoes. We compare pre-transition size between runners who developed bone marrow edema to those who did not. 37 runners were randomly assigned to the Vibram FiveFingers™ group (n=18) or control group (n=19). Runners' bone marrow edema and intrinsic foot muscle size were measured at baseline and after 10 weeks. Total running volume was maintained by all runners. A significant increase in abductor hallucis cross-sectional area of 10.6% occurred in the Vibram FiveFingers™ group compared to the control group (p=0.01). There was no significant change in any of the other muscles examined (p>0.05). 8 of the Vibram FiveFingers™ runners, and 1 control runner developed bone marrow edema. Those who developed bone marrow edema, primarily women, had significantly smaller size in all assessed muscles (p≤0.05). Size of intrinsic foot muscles appears to be important in safely transitioning to minimalist shoe running. Perhaps intrinsic foot muscle strengthening may benefit runners wanting to transition to minimalist shoes. © Georg Thieme Verlag KG Stuttgart · New York.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okano, Junko, E-mail: jokano@belle.shiga-med.ac.jp; Kojima, Hideto; Katagi, Miwako

Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP{supmore » +}) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP{sup +} cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR. - Highlights: • Bone marrow-derived cells (BMDCs) migrate in the epidermis due to ionizing radiation (IR). • BMDCs dissociate from the epidermis-dermis junction in preparing epidermal sheets. • The doses of IR determine the location and the number of migrating BMDCs in the skin.« less

Association between the rapid shallow breathing index and extubation success in patients with traumatic brain injury

PubMed Central

dos Reis, Helena França Correia; Almeida, Mônica Lajana Oliveira; da Silva, Mário Ferreira; Moreira, Julião Oliveira; Rocha, Mário de Seixas

2013-01-01

Objective To investigate the association between the rapid shallow breathing index and successful extubation in patients with traumatic brain injury. Methods This study was a prospective study conducted in patients with traumatic brain injury of both genders who underwent mechanical ventilation for at least two days and who passed a spontaneous breathing trial. The minute volume and respiratory rate were measured using a ventilometer, and the data were used to calculate the rapid shallow breathing index (respiratory rate/tidal volume). The dependent variable was the extubation outcome: reintubation after up to 48 hours (extubation failure) or not (extubation success). The independent variable was the rapid shallow breathing index measured after a successful spontaneous breathing trial. Results The sample comprised 119 individuals, including 111 (93.3%) males. The average age of the sample was 35.0±12.9 years old. The average duration of mechanical ventilation was 8.1±3.6 days. A total of 104 (87.4%) participants achieved successful extubation. No association was found between the rapid shallow breathing index and extubation success. Conclusion The rapid shallow breathing index was not associated with successful extubation in patients with traumatic brain injury. PMID:24213084

MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women.

PubMed

Shen, W; Chen, J; Punyanitya, M; Shapses, S; Heshka, S; Heymsfield, S B

2007-05-01

Recent studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Previous research using regional magnetic resonance spectroscopy methods to measure BMAT has reported inconsistent findings on the relationship between BMAT and dual-energy absorptiometry (DXA)-measured bone mineral density (BMD). In the present study, total body and pelvic BMAT were evaluated in 56 healthy women (age 18-88 yrs, mean +/- SD, 47.4 +/- 17.6 yrs; BMI, 24.3 +/- 4.2 kg/m(2)) with T1-weighted whole-body magnetic resonance imaging (MRI). BMD was measured using the whole-body DXA mode (GE Lunar DPX, software version 4.7). A strong negative correlation was observed between pelvic BMAT and BMD (total-body BMD, R = -0.743, P < 0.001; pelvic BMD, R = -0.646, P < 0.001), and between total-body BMAT and BMD (total-body BMD, R = -0.443, P < 0.001; pelvic BMD, R = -0.308, P < 0.001). The inverse association between pelvic BMAT and BMD remained strong after adjusting for age, weight, total body fat, and menopausal status (partial correlation: total-body BMD, R = -0.553, P < 0.001; pelvic BMD, R = -0.513, P < 0.001). BMAT was also highly correlated with age (pelvic BMAT, R = 0.715, P < 0.001; total-body BMAT, R = 0.519, P < 0.001). MRI-measured BMAT is thus strongly inversely correlated with DXA-measured BMD independent of other predictor variables. These observations, in the context of DXA technical concerns, support the growing evidence linking BMAT with low bone density.

Origins of endothelial and osteogenic cells in the subcutaneous collagen gel implant.

PubMed

Bilic-Curcic, I; Kalajzic, Z; Wang, L; Rowe, D W

2005-11-01

The interdependent relationship between vascular endothelial cells and osteoblasts during bone formation and fracture healing has been long appreciated. This paper reports a heterotopic implant model using FGF-2-expanded bone marrow stromal cells (BMSC) derived from Tie2eGFP (endothelial marker) and pOBCol3.6GFPcyan or topaz (early osteoblast marker) transgenic mice to appreciate the host/donor relationships of cells participating in the process of heterotopic bone formation. The study included various combinations of Tie2eGFP and pOBCol3.6GFPcyan and topaz transgenics as BMSC or whole bone marrow (WBM) donors and also as recipients. Rat tail collagen was used as a carrier of donor cells and implantation was done in lethally irradiated mice rescued with WBM injection. Development of ossicles in the implants was followed weekly during the 4- to 5-week long post-implantation period. By 4-5 weeks after total body irradiation (TBI) and implantation, a well-formed bone spicule had developed that was invested with bone marrow. Experiments showed absolute dominance of donor-derived cells in the formation of endothelial-lined vessels inside the implants as well as the marrow stromal-derived osteogenic cells. Host-derived fibroblasts and osteogenic cells were confined to the fibrous capsule surrounding the implant. In addition, cells lining the endosteal surface of newly formed marrow space carrying a pOBCol3.6GFP marker were observed that were contributed by WBM donor cells and the host. Thus, FGF-2-expanded BMSC appear to be a source of endothelial and osteogenic progenitor cells capable of eliciting heterotopic bone formation independent of cells from the host. This model should be useful for understanding the interactions between these two cell types that control osteogenic differentiation in vivo.

Bone marrow produces sufficient alloreactive natural killer (NK) cells in vivo to cure mice from subcutaneously and intravascularly injected 4T1 breast cancer.

PubMed

van Gelder, Michel; Vanclée, Ariane; van Elssen, Catharina H M J; Hupperets, Pierre; Wieten, Lotte; Bos, Gerard M

2017-02-01

Administration of 5 million alloreactive natural killer (NK) cells after low-dose chemo-irradiation cured mice of 4T1 breast cancer, supposedly dose dependent. We now explored the efficacy of bone marrow as alternative in vivo source of NK cells for anti-breast cancer treatment, as methods for in vitro clinical scale NK cell expansion are still in developmental phases. Progression-free survival (PFS) after treatment with different doses of spleen-derived alloreactive NK cells to 4T1-bearing Balb/c mice was measured to determine a dose-response relation. The potential of bone marrow as source of alloreactive NK cells was explored using MHC-mismatched mice as recipients of 4T1. Chemo-irradiation consisted of 2× 2 Gy total body irradiation and 200 mg/kg cyclophosphamide. Antibody-mediated in vivo NK cell depletion was applied to demonstrate the NK cell's role. Administration of 2.5 instead of 5 million alloreactive NK cells significantly reduced PFS, evidencing dose responsiveness. Compared to MHC-matched receivers of subcutaneous 4T1, fewer MHC-mismatched mice developed tumors, which was due to NK cell alloreactivity because in vivo NK cell depletion facilitated tumor growth. Application of low-dose chemo-irradiation increased plasma levels of NK cell-activating cytokines, NK cell activity and enhanced NK cell-dependent elimination of subcutaneous tumors. Intravenously injected 4T1 was eliminated by alloreactive NK cells in MHC-mismatched recipients without the need for chemo-irradiation. Bone marrow is a suitable source of sufficient alloreactive NK cells for the cure of 4T1 breast cancer. These results prompt clinical exploration of bone marrow transplantation from NK-alloreactive MHC-mismatched donors in patients with metastasized breast cancer.

Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

PubMed

Viehl, Carsten T; Weixler, Benjamin; Guller, Ulrich; Dell-Kuster, Salome; Rosenthal, Rachel; Ramser, Michaela; Banz, Vanessa; Langer, Igor; Terracciano, Luigi; Sauter, Guido; Oertli, Daniel; Zuber, Markus

2017-05-01

The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Soluble stem cell factor receptor (CD117) and IL-2 receptor alpha chain (CD25) levels in the plasma of patients with mastocytosis: relationships to disease severity and bone marrow pathology.

PubMed

Akin, C; Schwartz, L B; Kitoh, T; Obayashi, H; Worobec, A S; Scott, L M; Metcalfe, D D

2000-08-15

Systemic mastocytosis is a disease of mast cell proliferation that may be associated with hematologic disorders. There are no features on examination that allow the diagnosis of systemic disease, and mast cell-derived mediators, which may be elevated in urine or blood, may also be elevated in individuals with severe allergic disorders. Thus, the diagnosis usually depends on results of bone marrow biopsy. To facilitate evaluation, surrogate markers of the extent and severity of the disease are needed. Because of the association of mastocytosis with hematologic disease, plasma levels were measured for soluble KIT (sKIT) and soluble interleukin-2 receptor alpha chain (sCD25), which are known to be cleaved in part from the mast cell surface and are elevated in some hematologic malignancies. Results revealed that levels of both soluble receptors are increased in systemic mastocytosis. Median plasma sKIT concentrations as expressed by AU/mL (1 AU = 1.4 ng/mL) were as follows: controls, 176 (n = 60); urticaria pigmentosa without systemic involvement, 194 (n = 8); systemic indolent mastocytosis, 511 (n = 30); systemic mastocytosis with an associated hematologic disorder, 1320 (n = 7); aggressive mastocytosis, 3390 (n = 3). Plasma sCD25 levels were elevated in systemic mastocytosis; the highest levels were associated with extensive bone marrow involvement. Levels of sKIT correlated with total tryptase levels, sCD25 levels, and bone marrow pathology. These results demonstrate that sKIT and sCD25 are useful surrogate markers of disease severity in patients with mastocytosis and should aid in diagnosis, in the selection of those needing a bone marrow biopsy, and in the documentation of disease progression. (Blood. 2000;96:1267-1273)

Amelioration of radiation-induced pulmonary fibrosis by a water-soluble bifunctional sulfoxide radiation mitigator (MMS350).

PubMed

Kalash, Ronny; Epperly, Michael W; Goff, Julie; Dixon, Tracy; Sprachman, Melissa M; Zhang, Xichen; Shields, Donna; Cao, Shaonan; Franicola, Darcy; Wipf, Peter; Berhane, Hebist; Wang, Hong; Au, Jeremiah; Greenberger, Joel S

2013-11-01

A water-soluble ionizing radiation mitigator would have considerable advantages for the management of acute and chronic effects of ionizing radiation. We report that a novel oxetanyl sulfoxide (MMS350) is effective both as a protector and a mitigator of clonal mouse bone marrow stromal cell lines in vitro, and is an effective in vivo mitigator when administered 24 h after 9.5 Gy (LD100/30) total-body irradiation of C57BL/6NHsd mice, significantly improving survival (P = 0.0097). Furthermore, MMS350 (400 μM) added weekly to drinking water after 20 Gy thoracic irradiation significantly decreased: expression of pulmonary inflammatory and profibrotic gene transcripts and proteins; migration into the lungs of bone marrow origin luciferase+/GFP+ (luc+/GFP+) fibroblast progenitors (in both luc+ marrow chimeric and luc+ stromal cell line injected mouse models) and decreased radiation-induced pulmonary fibrosis (P < 0.0001). This nontoxic and orally administered small molecule may be an effective therapeutic in clinical radiotherapy and as a counter measure against the acute and chronic effects of ionizing radiation.

Amelioration of Radiation-Induced Pulmonary Fibrosis by a Water-Soluble Bifunctional Sulfoxide Radiation Mitigator (MMS350)

PubMed Central

Kalash, Ronny; Epperly, Michael W.; Goff, Julie; Dixon, Tracy; Sprachman, Melissa M.; Zhang, Xichen; Shields, Donna; Cao, Shaonan; Franicola, Darcy; Wipf, Peter; Berhane, Hebist; Wang, Hong; Au, Jeremiah; Greenberger, Joel S.

2014-01-01

A water-soluble ionizing radiation mitigator would have considerable advantages for the management of acute and chronic effects of ionizing radiation. We report that a novel oxetanyl sulfoxide (MMS350) is effective both as a protector and a mitigator of clonal mouse bone marrow stromal cell lines in vitro, and is an effective in vivo mitigator when administered 24 h after 9.5 Gy (LD100/30) total-body irradiation of C57BL/6NHsd mice, significantly improving survival (P =0.0097). Furthermore, MMS350 (400 μM) added weekly to drinking water after 20 Gy thoracic irradiation significantly decreased: expression of pulmonary inflammatory and profibrotic gene transcripts and proteins; migration into the lungs of bone marrow origin luciferase+/GFP+ (luc+/GFP+) fibroblast progenitors (in both luc+ marrow chimeric and luc+ stromal cell line injected mouse models) and decreased radiation-induced pulmonary fibrosis (P < 0.0001). This nontoxic and orally administered small molecule may be an effective therapeutic in clinical radiotherapy and as a counter measure against the acute and chronic effects of ionizing radiation. PMID:24125487

Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells

NASA Technical Reports Server (NTRS)

Ichiki, A. T.; Gibson, L. A.; Jago, T. L.; Strickland, K. M.; Johnson, D. L.; Lange, R. D.; Allebban, Z.

1996-01-01

The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

Does an injection of a stromal vascular fraction containing adipose-derived mesenchymal stem cells influence the outcomes of marrow stimulation in osteochondral lesions of the talus? A clinical and magnetic resonance imaging study.

PubMed

Kim, Yong Sang; Lee, Ho Jin; Choi, Yun Jin; Kim, Yong Il; Koh, Yong Gon

2014-10-01

Marrow stimulation for the treatment of osteochondral lesions of the talus (OLTs) is controversial in patients with poor prognostic factors of OLTs. Currently, mesenchymal stem cells (MSCs) are expected to biologically augment the treatment of OLTs. To compare the clinical and magnetic resonance imaging (MRI) outcomes between an injection of MSCs with marrow stimulation and marrow stimulation alone in patients with OLTs. Cohort study; Level of evidence, 3. A total of 49 patients (50 ankles) with OLTs underwent follow-up MRI after arthroscopic treatment. Among these 50 ankles, 26 underwent marrow stimulation alone (conventional group), and 24 underwent marrow stimulation with an injection of a stromal vascular fraction (SVF) containing MSCs (MSC group). Clinical outcomes were evaluated according to the visual analog scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Tegner activity scale. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used for the MRI evaluation of repaired lesions. The mean VAS score, AOFAS score, and Tegner score improved from 7.1 ± 1.2, 68.5 ± 5.6, and 3.4 ± 0.6 to 3.9 ± 0.8, 78.3 ± 4.9, and 3.5 ± 0.8, respectively, in the conventional group and from 7.1 ± 0.8, 67.7 ± 4.7, and 3.4 ± 0.5 to 3.2 ± 0.8, 83.3 ± 7.0, and 3.9 ± 0.7, respectively, in the MSC group. All clinical outcomes, including the VAS, AOFAS, and Tegner scores, improved significantly in the MSC group compared with the conventional group (P = .003, .009, and .041, respectively). There was a significant difference (P = .037) in the mean MOCART score between the conventional and MSC groups (49.4 ± 16.6 vs 62.1 ± 21.8, respectively), and significant correlations of the MOCART score with clinical outcomes were found in both groups (P < .05). Patient age (≥46.1 years), large lesion size (≥151.2 mm(2)), and the presence of subchondral cysts were associated with a worse MOCART score in the conventional group (P = .015, .004, and .013, respectively) but not in the MSC group. Clinical and MRI outcomes of an injection of an SVF containing MSCs with marrow stimulation were encouraging, compared with marrow stimulation alone, for the treatment of OLTs. Therefore, an injection of an SVF containing MSCs with marrow stimulation should be considered as a treatment for OLTs, even when poor prognostic factors, including older age, large-sized lesion, or the presence of subchondral cysts, exist. © 2014 The Author(s).

Spatial distribution of marine fishes along a cross-shelf gradient containing a continuum of mangrove seagrass coral reefs off southwestern Puerto Rico

NASA Astrophysics Data System (ADS)

Aguilar-Perera, Alfonso; Appeldoorn, Richard S.

2008-01-01

Despite an extensive study of the fish community off southwestern Puerto Rico, little information is available on the fish spatial distribution along an inshore-offshore, cross-shelf gradient containing a continuum of mangrove-seagrass-coral reefs. We investigated the spatial distribution of reef-associated fish species using a stratified sampling procedure. A total of 52,138 fishes were recorded, representing 102 species belonging to 32 families. Significant differences in mean fish density were evident among strata. Mean densities at shallow fore reefs and deep fore reefs (Romero key) were significantly higher compared to the rest of strata along the gradient. Mean densities of fishes in mangroves and seagrass (Montalva Bay) were comparable to those at shallow back reefs and deep fore reefs offshore (Turrumote), but lower to those inshore (Romero); the lowest fish densities were found in mangroves and seagrass (Montalva Bay) and seagrass (Romero and Corral). At least 17 species, in 7 families, were among the most common in terms of relative abundance representing 76% of the total individuals sampled. A detrended correspondence analysis (DCA) applied to more abundant fish species showed a spatial pattern in density distribution. Three major groupings were evident corresponding to mangroves and seagrass (Montalva Bay), shallow and deep reefs (Romero), and shallow and deep reefs (Corral and Turrumote). A cluster analysis on mean fish densities of the more abundant species revealed a consistent spatial distribution according to biotope by separating the ichthyofauna associated with mangroves, seagrass and that of shallow (back and fore) reefs, and deep fore reefs.

A long-term follow-up of 33 patients with non-Hodgkin's lymphoma who received the BEAM high-dose intensification regimen with cytokine support only and no transplant.

PubMed

Laporte, J Ph; Yeshurun, M; Fouillard, L; Labopin, M; Cailliot, C; Lesage, S; Isnard, F; Najman, A; Gorin, N-C

2004-10-01

High-dose intensification and autologous stem-cell transplantation (ASCT) is widely used to consolidate patients with non-Hodgkin's lymphoma (NHL), who have reached a stage of minimal residual disease. However, patients with persisting marrow and/or blood involvement and those who fail peripheral blood hemopoietic progenitor mobilization are excluded from ASCT. For such patients with no available graft to infuse, we developed 15 years ago, before the anti-CD20 monoclonal antibody therapeutic era, the use of the BEAM pretransplant regimen followed only by the administration of three cytokines (erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor). We report here on the long-term follow-up of 33 patients treated with this approach. In all, 33 NHL patients underwent the BEAM (carmustine, VP-16, cytosine-arabinoside, melphalan) followed by the administration of the three cytokines from January 1994-2000. A backup marrow, albeit infiltrated by tumor cells, had been collected earlier and stored in all. A total of 30 patients (91%) recovered normal hematopoiesis. In total, 32 patients (97%) recovered neutrophils (>500/microl) at a median of 19 days and 30 patients (91%) recovered platelets (>20,000/microl) at a median of 26 days. Age, richness of backup graft and blood-hemoglobin level at intensification had an impact on the time for hematopoietic recovery (P=0.014, P=0.014, P=0.048). The median follow-up was 62 months. Five patients died from toxicity related to the procedure. Eight patients relapsed and died. A total of 20 patients (61%) are alive, 16 (49%) in complete remission. A 5-year disease-free survival was 52+/-9%, relapse incidence 35+/-16%, mortality due to the procedure 12+/-12% and overall survival 61+/-10%. The BEAM regimen is not myeloablative. The BEAM+3CK procedure is a feasible therapeutic option that has shown efficacy in poor risk NHL patients who were not eligible for autografting because of persisting marrow/blood tumor contamination, or poor hemopoietic progenitor harvesting. It is unclear today whether some of these patients would have cleared their marrow/peripheral blood with the additional use of anti-CD20 treatment, thereby making the classical approach (BEAM followed by the infusion of a clean autograft) feasible.

Generalized energy and potential enstrophy conserving finite difference schemes for the shallow water equations

NASA Technical Reports Server (NTRS)

Abramopoulos, Frank

1988-01-01

The conditions under which finite difference schemes for the shallow water equations can conserve both total energy and potential enstrophy are considered. A method of deriving such schemes using operator formalism is developed. Several such schemes are derived for the A-, B- and C-grids. The derived schemes include second-order schemes and pseudo-fourth-order schemes. The simplest B-grid pseudo-fourth-order schemes are presented.

Shallow Water Acoustic Experiments and Preliminary Planning for FY06 Fieldwork

DTIC Science & Technology

2011-03-21

To) 5/1/2005-12/31/2010 4. TITLE AND SUBTITLE Shallow Water Acoustic Experiments and Preliminary Planning for FY06 Fieldwork 5a. CONTRACT NUMBERS...numerical computations show horizontal interference patterns within the duct. Richly de - tailed sound radiation fields are predicted at locations far...4) for the vertical modal amplitude Tm at x^L is now de - scribed in detail. First, the assumption of total transmission at the open-ended

Sediment dynamics in a large shallow lake characterized by seasonal flood pulse in Southeast Asia.

PubMed

Siev, Sokly; Yang, Heejun; Sok, Ty; Uk, Sovannara; Song, Layheang; Kodikara, Dilini; Oeurng, Chantha; Hul, Seingheng; Yoshimura, Chihiro

2018-08-01

Most of studies on sediment dynamics in stable shallow lakes focused on the resuspension process as it is the dominant process. However, understanding of sediment dynamics in a shallow lake influenced by flood pulse is unclear. We tested a hypothesis that floodplain vegetation plays as a significant role in lessening the intensity of resuspension process in a shallow lake characterized by the flood pulse system. Therefore, this study aimed to investigate sediment dynamics in this type of shallow lake. The target was Tonle Sap Lake (TSL), which is a large shallow lake influenced by a flood pulse system of Mekong River located in Southeast Asia. An extensive and seasonal sampling survey was conducted to measure total suspended solid (TSS) concentrations, sedimentation and resuspension rates in TSL and its 4 floodplain areas. The study revealed that sedimentation process was dominant (TSS ranged: 3-126mgL -1 ) in the high water period (September-December) while resuspension process was dominant (TSS ranged: 4-652mgL -1 ) only in the low water period (March-June). In addition, floodplain vegetation reduced the resuspension of sediment (up to 26.3%) in water. The implication of the study showed that resuspension is a seasonally dominant process in shallow lake influenced by the flood pulse system at least for the case of TSL. Copyright © 2018 Elsevier B.V. All rights reserved.

Dissolved methane occurrences in aquifers in the footprint of Texas shale plays and their controls

NASA Astrophysics Data System (ADS)

Nicot, J. P.; Mickler, P. J.; Larson, T.; Darvari, R.; Smyth, R. C.

2015-12-01

Many constituents typically associated with oil and gas production, such as methane and higher-order hydrocarbons, exist naturally in shallow groundwater. Recent studies of aquifers in the footprint of several gas plays across the US have showed that (1) dissolved thermogenic methane may or may not be present in the shallow subsurface and (2) shallow thermogenic methane could be naturally occurring and emplaced through mostly vertical migration over geologic time and is not necessarily a consequence of gas production from a gas play. A total of 800+ water wells have been sampled across the state of Texas to characterize shallow methane in fresh-water aquifers overlying shale plays and other tight formations (Barnett, Eagle Ford, Haynesville shale areas as well as in the Delaware Basin of West Texas). Analytical results suggest that dissolved methane is not widespread in shallow groundwater and that, when present at concentration greater than 10 mg/L, is often of natural but thermogenic or mixed origin according to the isotopic signature and to the presence of other light hydrocarbons.

Hell and High Water: Diminished Septic System Performance in Coastal Regions Due to Climate Change

PubMed Central

Cooper, Jennifer A.; Loomis, George W.; Amador, Jose A.

2016-01-01

Climate change may affect the ability of soil-based onsite wastewater treatment systems (OWTS) to treat wastewater in coastal regions of the Northeastern United States. Higher temperatures and water tables can affect treatment by reducing the volume of unsaturated soil and oxygen available for treatment, which may result in greater transport of pathogens, nutrients, and biochemical oxygen demand (BOD5) to groundwater, jeopardizing public and aquatic ecosystem health. The soil treatment area (STA) of an OWTS removes contaminants as wastewater percolates through the soil. Conventional STAs receive wastewater from the septic tank, with infiltration occurring deeper in the soil profile. In contrast, shallow narrow STAs receive pre-treated wastewater that infiltrates higher in the soil profile, which may make them more resilient to climate change. We used intact soil mesocosms to quantify the water quality functions of a conventional and two types of shallow narrow STAs under present climate (PC; 20°C) and climate change (CC; 25°C, 30 cm elevation in water table). Significantly greater removal of BOD5 was observed under CC for all STA types. Phosphorus removal decreased significantly from 75% (PC) to 66% (CC) in the conventional STA, and from 100% to 71–72% in shallow narrow STAs. No fecal coliform bacteria (FCB) were released under PC, whereas up to 17 and 20 CFU 100 mL-1 were released in conventional and shallow narrow STAs, respectively, under CC. Total N removal increased from 14% (PC) to 19% (CC) in the conventional STA, but decreased in shallow narrow STAs, from 6–7% to less than 3.0%. Differences in removal of FCB and total N were not significant. Leaching of N in excess of inputs was also observed in shallow narrow STAs under CC. Our results indicate that climate change can affect contaminant removal from wastewater, with effects dependent on the contaminant and STA type. PMID:27583363

Hell and High Water: Diminished Septic System Performance in Coastal Regions Due to Climate Change.

PubMed

Cooper, Jennifer A; Loomis, George W; Amador, Jose A

2016-01-01

Climate change may affect the ability of soil-based onsite wastewater treatment systems (OWTS) to treat wastewater in coastal regions of the Northeastern United States. Higher temperatures and water tables can affect treatment by reducing the volume of unsaturated soil and oxygen available for treatment, which may result in greater transport of pathogens, nutrients, and biochemical oxygen demand (BOD5) to groundwater, jeopardizing public and aquatic ecosystem health. The soil treatment area (STA) of an OWTS removes contaminants as wastewater percolates through the soil. Conventional STAs receive wastewater from the septic tank, with infiltration occurring deeper in the soil profile. In contrast, shallow narrow STAs receive pre-treated wastewater that infiltrates higher in the soil profile, which may make them more resilient to climate change. We used intact soil mesocosms to quantify the water quality functions of a conventional and two types of shallow narrow STAs under present climate (PC; 20°C) and climate change (CC; 25°C, 30 cm elevation in water table). Significantly greater removal of BOD5 was observed under CC for all STA types. Phosphorus removal decreased significantly from 75% (PC) to 66% (CC) in the conventional STA, and from 100% to 71-72% in shallow narrow STAs. No fecal coliform bacteria (FCB) were released under PC, whereas up to 17 and 20 CFU 100 mL-1 were released in conventional and shallow narrow STAs, respectively, under CC. Total N removal increased from 14% (PC) to 19% (CC) in the conventional STA, but decreased in shallow narrow STAs, from 6-7% to less than 3.0%. Differences in removal of FCB and total N were not significant. Leaching of N in excess of inputs was also observed in shallow narrow STAs under CC. Our results indicate that climate change can affect contaminant removal from wastewater, with effects dependent on the contaminant and STA type.

Estimates of long-term water total phosphorus (TP) concentrations in three large shallow lakes in the Yangtze River basin, China.

PubMed

Wu, Pan; Qin, Boqiang; Yu, Ge

2016-03-01

The shallow lakes in the eastern China developed on alluvial plains with high-nutrient sediments, and most overflow into the Yangtze River with short hydraulic residence times, whereas they become eutrophic over long time periods. Assuming strong responses to hydrogeological changes in the basin, we attempted to determine the dynamic eutrophication history of these lakes. Although evaluation models for internal total phosphorus (TP) loading are widely used for deep lakes in Europe and North America, the accuracy of these models for shallow lakes that have smaller water volumes controlled by the geometrical morphology and greater basin area of alluvial plains is unknown. To describe the magnitude of changes in velocity of trophic state for the studied shallow lakes, we first evaluated the P retention model in relation to the major forces driving lake morphology, basin climate, and external discharge and then used the model to estimate changes in TP in three large shallow lakes (Taihu, Chao, and Poyang) over 60 years (1950-2009 AD). The observed levels of TP were verified against the relative error of the three lakes (<6.43 %) and Nash-Sutcliffe coefficients (0.67-0.75). The results showed that the predicted TP concentrations largely increased with hydraulic residence time, especially in extreme drought years, with a generally rising trend in trophic status. The simulated trophic state index showed that lakes Taihu and Poyang became eutrophic in the 1990s, whereas Lake Chao became eutrophic in the 1980s; lakes Taihu and Chao ultimately became hypereutrophic in the 2000s. The analysis suggested that the tropic status of the shallow lakes was affected by both the hydroclimate and geological sedimentation of the Yangtze River basin. This work will contribute to the development of an internal P loading model for further evaluating trophic states.

Smoldering Remediation of Coal-Tar-Contaminated Soil: Pilot Field Tests of STAR.

PubMed

Scholes, Grant C; Gerhard, Jason I; Grant, Gavin P; Major, David W; Vidumsky, John E; Switzer, Christine; Torero, Jose L

2015-12-15

Self-sustaining treatment for active remediation (STAR) is an emerging, smoldering-based technology for nonaqueous-phase liquid (NAPL) remediation. This work presents the first in situ field evaluation of STAR. Pilot field tests were performed at 3.0 m (shallow test) and 7.9 m (deep test) below ground surface within distinct lithological units contaminated with coal tar at a former industrial facility. Self-sustained smoldering (i.e., after the in-well ignition heater was terminated) was demonstrated below the water table for the first time. The outward propagation of a NAPL smoldering front was mapped, and the NAPL destruction rate was quantified in real time. A total of 3700 kg of coal tar over 12 days in the shallow test and 860 kg over 11 days in the deep test was destroyed; less than 2% of total mass removed was volatilized. Self-sustaining propagation was relatively uniform radially outward in the deep test, achieving a radius of influence of 3.7 m; strong permeability contrasts and installed barriers influenced the front propagation geometry in the shallow test. Reductions in soil hydrocarbon concentrations of 99.3% and 97.3% were achieved in the shallow and deep tests, respectively. Overall, this provides the first field evaluation of STAR and demonstrates that it is effective in situ and under a variety of conditions and provides the information necessary for designing the full-scale site treatment.

Phytoplankton Functional Groups Variation and Influencing Factors in a Shallow Temperate Lake.

PubMed

Tian, Chang; Hao, Daping; Pei, Haiyan; Doblin, Martina A; Ren, Ying; Wei, Jielin; Feng, Yawei

2018-06-01

  The present study was carried out in Luoma Lake, a shallow lake in temperate eastern China. Based on a two-year study, the dynamics of phytoplankton functional groups and influencing factors were analyzed. A total of 178 taxa were identified and sorted into 20 codons, according to the phytoplankton functional group classification. In order to find the environmental factors driving phytoplankton variations, fifteen groups were analyzed in detail using redundancy analysis. Groups P (Fragilaria crotonensis), X2 (Chlamydomonas globosa, C. microsphaera and Chroomonas acuta), and MP (Navicula rotaeana) were dominant during low temperature periods, whereas groups X2, S1 (Pseudanabaena limnetica), and W1 (Euglena sp.) were dominant during high temperature periods. Water temperature, total phosphorus, and ammonium were the significant driving factors explaining phytoplankton succession. Furthermore, total phosphorus and ammonium could be broadly used in risk management for potential algal blooms in Luoma Lake.

Environmental conditions in the Namskaket Marsh Area, Orleans, Massachusetts: A summary of studies by the U.S. Geological Survey, 1989–2011

USGS Publications Warehouse

Weiskel, Peter K.; Barbaro, Jeffrey R.; DeSimone, Leslie A.

2016-09-23

The tidal creek sampling stations established in the 1990s were resampled in 2003–4 and 2010–11 to evaluate potential effects of the treated wastewater plume on creek water quality. The annual medians of the 2011 biweekly nitrate and total dissolved nitrogen concentrations were determined for each station and compared to the annual medians of biweekly samples for the baseline years 1994, 1995, and 1996. At all stations, the 2011 median nitrate concentrations were within the range of medians for the 3 baseline years. A similar result was obtained for total dissolved nitrogen. We conclude that the 2011 creek samples, collected approximately 8 years after the shallow plume segment was first detected beneath the marsh, do not show evidence of elevated nitrate or total dissolved nitrogen concentrations attributable to discharge of either the shallow or deep segments of the treated wastewater plume.

Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis.

PubMed

Shabestari, M; Vik, J; Reseland, J E; Eriksen, E F

2016-10-01

Bone marrow lesions (BML), previously denoted bone marrow edema, are detected as water signals by magnetic resonance imaging (MRI). Previous histologic studies were unable to demonstrate any edematous changes at the tissue level. Therefore, our aim was to investigate the underlying biological mechanisms of the water signal in MRI scans of bone affected by BML. Tetracycline labeling in addition to water sensitive MRI scans of 30 patients planned for total hip replacement surgery was undertaken. Twenty-one femoral heads revealed BML on MRI, while nine were negative and used as controls (CON). Guided by the MRI images cylindrical biopsies were extracted from areas with BML in the femoral heads. Tissue sections from the biopsies were subjected to histomorphometric image analyses of the cancellous bone envelope. Patients with BML exhibited an average 40- and 18-fold increase of bone formation rate and mineralizing surface, respectively. Additionally, samples with BML demonstrated 2-fold reduction of marrow fat and 28-fold increase of woven bone. Immunohistochemical analysis showed a 4-fold increase of angiogenesis markers CD31 and von Willebrand Factor (vWF) in the BML-group compared to CON. This study indicates that BML are characterized by increased bone turnover, vascularity and angiogenesis in keeping with it being a reparatory process. Thus, the water signal, which is the hallmark of BML on MRI, is most probably reflecting increased tissue vascularity accompanying increased remodeling activity. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure

PubMed Central

Togni Filho, Paulo Henrique; Casagrande, João Luiz Marin; Lederman, Henrique Manoel

2017-01-01

Objective To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. Materials and Methods This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. Results A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient). The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. Conclusion In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population. PMID:28428651

MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women

PubMed Central

Chen, J.; Punyanitya, M.; Shapses, S.; Heshka, S.; Heymsfield, S. B.

2007-01-01

Introduction Recent studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Previous research using regional magnetic resonance spectroscopy methods to measure BMAT has reported inconsistent findings on the relationship between BMAT and dual-energy absorptiometry (DXA)-measured bone mineral density (BMD). Methods In the present study, total body and pelvic BMAT were evaluated in 56 healthy women (age 18–88 yrs, mean±SD, 47.4±17.6 yrs; BMI, 24.3±4.2 kg/m2) with T1-weighted whole-body magnetic resonance imaging (MRI). BMD was measured using the whole-body DXA mode (GE Lunar DPX, software version 4.7). Results A strong negative correlation was observed between pelvic BMAT and BMD (total-body BMD, R=− 0.743, P<0.001; pelvic BMD, R=− 0.646, P<0.001), and between total-body BMAT and BMD (total-body BMD, R=− 0.443, P<0.001; pelvic BMD, R=− 0.308, P < 0.001). The inverse association between pelvic BMAT and BMD remained strong after adjusting for age, weight, total body fat, and menopausal status (partial correlation: total-body BMD, R=− 0.553, P< 0.001; pelvic BMD, R=− 0.513, P<0.001). BMAT was also highly correlated with age (pelvic BMAT, R=0.715, P< 0.001; total-body BMAT, R=0.519, P<0.001). Conclusion MRI-measured BMAT is thus strongly inversely correlated with DXA-measured BMD independent of other predictor variables. These observations, in the context of DXA technical concerns, support the growing evidence linking BMAT with low bone density. PMID:17139464

Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

ClinicalTrials.gov

2018-03-27

Adult Acute Lymphoblastic Leukemia in Complete Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia in Complete Remission

What Is a Bone Marrow Transplant?

MedlinePlus

... Print this page My Cart What is a bone marrow transplant? A bone marrow transplant is a ... blood.” – Edmund Waller, MD, PHD What is a bone marrow transplant? A bone marrow transplant is a ...

[Relation between distribution of phosphorus form in the sediment of typical urban shallow lakes and eutrophication].

PubMed

Wang, Chao; Zou, Li-Min; Wang, Pei-Fang; Lin, Zhi-Ping

2008-05-01

The forms of phosphorus in the surface sediments were extracted and determined sequentially with ethylene dinitrilo tetracetic acid (EDTA) technique in three urban shallow lakes: Lake Xuanwu, Lake Mochou and Lake Daming. The results showed that the iron and calcium-bound phosphate, about accounting for 80%, were the main forms of total phosphorus. The contents of iron bound phosphate in Lake Xuanwu and Lake Mochou were higher than that of Lake Daming, reaching 30%-40%. The organic phosphorus existed mainly in the form of alkali extractable phosphorus, while the contents of acid extractable organic phosphorus were low. However, the proportion of acid extractable organic phosphorus to the total phosphorus can indicate the degree of lake eutrophication.

NOS2 deficiency has no influence on the radiosensitivity of the hematopoietic system.

PubMed

Li, Chengcheng; Luo, Yi; Shao, Lijian; Meng, Aimin; Zhou, Daohong

2018-01-01

Previous studies have shown that inhibition of inducible NO synthase (NOS2 or iNOS) with an inhibitor can selectively protect several normal tissues against radiation during radiotherapy. However, the role of NOS2 in ionizing radiation (IR)-induced bone marrow (BM) suppression is unknown and thus was investigated in the present study using NOS2 - / - and wild-type mice 14 days after they were exposed to a sublethal dose of total body irradiation (TBI). The effects of different doses of IR (1, 2 and 4 Gy) on the apoptosis and colony-forming ability of bone marrow cells from wild-type (WT) and NOS2 - / - mice were investigated in vitro. In addition, we exposed NOS2 - / - mice and WT mice to 6-Gy TBI or sham irradiation. They were euthanized 14 days after TBI for analysis of peripheral blood cell counts and bone marrow cellularity. Colony-forming unit-granulocyte and macrophage, burst-forming unit-erythroid and CFU-granulocyte, erythroid, macrophage in bone marrow cells from the mice were determined to evaluate the function of hematopoietic progenitor cells (HPCs), and the ability of hematopoietic stem cells (HSCs) to self-renew was analysed by the cobblestone area forming cell assay. The cell cycling of HPCs and HSCs were measured by flow cytometry. Exposure to 2 and 4 Gy IR induced bone marrow cell apoptosis and inhibited the proliferation of HPCs in vitro. However, there was no difference between the cells from WT mice and NOS2 - / - mice in response to IR exposure in vitro. Exposure of WT mice and NOS2 - / - mice to 6 Gy TBI decreased the white blood cell, red blood cell, and platelet counts in the peripheral blood and bone marrow mononuclear cells, and reduced the colony-forming ability of HPCs (P < 0.05), damaged the clonogenic function of HSCs. However, these changes were not significantly different in WT and NOS2 - / - mice. These data suggest that IR induces BM suppression in a NOS2-independent manner.

Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandmaier, B M.; Bethge, W A.; Wilbur, D. Scott

To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external- beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (46 minutes) alpha-emitter Bi-213 conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, andmore » liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg[3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg[133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). Therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs achieved prompt engraftment and stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results form the basis for additional studies in animals and the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity.« less

Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

PubMed

Bastos, C M; Araújo, I M; Nogueira-Barbosa, M H; Salmon, C E G; de Paula, F J A; Troncon, L E A

2017-07-01

Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

The effect of refrigeration of bone marrow and peripheral blood on cytogenetic analysis.

PubMed

Martin, P K; Rowley, J D

1986-07-01

Bone marrow samples from patients with various hematologic disorders were stored at 4 degrees C for up to 5 d before the establishment of a 24-h culture. We tested various factors, including storage time, colony stimulating factor, and methotrexate in an effort to improve metaphase and chromosome quality. Cytogenetic findings for various hematologic diseases were compared in a total of 201 cultures. Cold storage for up to 3 d did not seem to adversely affect the number of mitoses or the quality of chromosome banding when cells were cultured in a system that used both colony stimulating factor and methotrexate. In samples studied in parallel, clonal abnormalities were noted as frequently in cells stored in the cold as in those processed directly.

Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

USGS Publications Warehouse

Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

2012-01-01

Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague–Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p < 0.05) the activities of plasma alanine aminotransferase–glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase–glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p < 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague–Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.

A Comparison between Deep and Shallow Stress Fields in Korea Using Earthquake Focal Mechanism Inversions and Hydraulic Fracturing Stress Measurements

NASA Astrophysics Data System (ADS)

Lee, Rayeon; Chang, Chandong; Hong, Tae-kyung; Lee, Junhyung; Bae, Seong-Ho; Park, Eui-Seob; Park, Chan

2016-04-01

We are characterizing stress fields in Korea using two types of stress data: earthquake focal mechanism inversions (FMF) and hydraulic fracturing stress measurements (HF). The earthquake focal mechanism inversion data represent stress conditions at 2-20 km depths, whereas the hydraulic fracturing stress measurements, mostly conducted for geotechnical purposes, have been carried out at depths shallower than 1 km. We classified individual stress data based on the World Stress Map quality ranking scheme. A total of 20 FMF data were classified into A-B quality, possibly representing tectonic stress fields. A total of 83 HF data out of compiled 226 data were classified into B-C quality, which we use for shallow stress field characterization. The tectonic stress, revealed from the FMF data, is characterized by a remarkable consistency in its maximum stress (σ1) directions in and around Korea (N79±2° E), indicating a quite uniform deep stress field throughout. On the other hand, the shallow stress field, represented by HF data, exhibits local variations in σ1 directions, possibly due to effects of topography and geologic structures such as faults. Nonetheless, there is a general similarity in σ1 directions between deep and shallow stress fields. To investigate the shallow stress field statistically, we follow 'the mean orientation and wavelength analysis' suggested by Reiter et al. (2014). After the stress pattern analysis, the resulting stress points distribute sporadically over the country, not covering the entire region evenly. In the western part of Korea, the shallow σ1directions are generally uniform with their search radius reaching 100 km, where the average stress direction agrees well with those of the deep tectonic stress. We note two noticeable differences between shallow and deep stresses in the eastern part of Korea. First, the shallow σ1 orientations are markedly non-uniform in the southeastern part of Korea with their search radius less than 25 km. In this region, the average σ1orientation based on the entire B-C quality stress data is calculated to be 77±37° ; however, the average orientation is somewhat meaningless because of the high standard deviation. The southeastern part of Korea consists mainly of Cretaceous sedimentary basin, geologically younger than the rest of the country, where regional scale faults are intensely populated. The highly scattered stress directions in this region may represent the effect of the geologic structures on shallow stress field. Second, shallow σ1 directions in the northeastern part of Korea strike consistently to 135±12° , which is deviated by as much as 56° from the deep tectonic stress direction. This region is characterized by high altitude mountainous topography (an elevation of an order of 1 km) with its major ridge axis in the NW-SE direction. We interpret, as a rule of thumb, that the ridge-perpendicular shallow horizontal stress components may be weak, leading to the ridge-parallel components to be the maximum. Overall, there are similarity and also difference between shallow and deep stress fields. Thus, it will be necessary to differentiate the strategy to tackle the stress-related problems based on their natures.

Building America Case Study: Pilot Demonstration of Phased Energy Efficiency Retrofits: Shallow Retrofit Results, Central and South Florida

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-02-22

The Florida Solar Energy Center (FSEC), in collaboration with Florida Power & Light (FPL), is pursuing a phased residential energy-efficiency retrofit program in Florida. Researchers are looking to establish the impacts of technologies of two retrofit packages -- shallow and deep -- on annual energy and peak energy reductions. Sixty homes have been instrumented to record total house power and detailed energy end-use data on all appliances as well as household interior temperature and relative humidity conditions.

Building America Case Study: Pilot Demonstration of Phased Energy Efficiency Retrofits: Shallow Retrofit Results, Central and South Florida

DOE Office of Scientific and Technical Information (OSTI.GOV)

D. Parker, K. Sutherland, D. Chasar, J. Montemurno, B. Amos, J. Kono

2017-02-01

The Florida Solar Energy Center (FSEC), in collaboration with Florida Power & Light (FPL), is pursuing a phased residential energy-efficiency retrofit program in Florida. Researchers are looking to establish the impacts of technologies of two retrofit packages -- shallow and deep -- on annual energy and peak energy reductions. Sixty homes have been instrumented to record total house power and detailed energy end-use data on all appliances as well as household interior temperature and relative humidity conditions.

Mastocytosis: magnetic resonance imaging patterns of marrow disease.

PubMed

Avila, N A; Ling, A; Metcalfe, D D; Worobec, A S

1998-03-01

To report the bone marrow MRI findings of patients with mastocytosis and correlate them with clinical, pathologic, and radiographic features. Eighteen patients with mastocytosis had T1-weighted spin echo and short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR pattern of marrow disease was classified according to intensity and uniformity and was correlated with the clinical category of mastocytosis, bone marrow biopsy results, and radiographic findings. Two patients had normal MRI scans and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and abnormal marrow biopsies. There were several different MR patterns of marrow involvement; none was specifically associated with any given clinical category of mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those, 13 with abnormal MRI scans and abnormal marrow biopsies had the following radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia (one). While radiographs are very insensitive for the detection of marrow abnormalities in mastocytosis, MRI is very sensitive and may display several different patterns of marrow involvement.

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

PubMed

Kook, H; Goldman, F; Padley, D; Giller, R; Rumelhart, S; Holida, M; Lee, N; Peters, C; Comito, M; Huling, D; Trigg, M

1996-08-01

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

The Prolonged Life-Span of Alveolar Macrophages

PubMed Central

Murphy, Jaime; Summer, Ross; Wilson, Andrew A.; Kotton, Darrell N.; Fine, Alan

2008-01-01

To further examine the half-life of alveolar macrophages, chimeric CD 45.2 mice were generated through bone marrow transplantation of donor CD 45.1 cells. Before administration of donor cells, recipient mice were divided into two cohorts: the first cohort received total body irradiation; the second cohort also received irradiation—however, the thorax, head, and upper extremities were shielded with lead. Flow cytometric analysis was then performed on blood, peritoneal, and bronchoalveolar lavage cells over time to quantify engraftment. The data generated for the unshielded cohort of mice revealed a macrophage half-life of 30 days. In the shielded cohort, however, we found that by 8 months there was negligible replacement of recipient alveolar macrophages by donor cells, despite reconstitution of the blood and peritoneum by donor bone marrow. Consistent with these findings, the mean fluorescent intensity of alveolar macrophages remained stable over a 4-week period after in vivo PKH26 dye loading. Together, these data show that previous alveolar macrophage half-life studies were confounded by the fact that they did not account for the toxic effects of irradiation conditioning regimens, and demonstrate that the bone marrow does not significantly contribute to the alveolar macrophage compartment during steady-state conditions. PMID:18192503

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 ...

Assessment of quality and geochemical processes occurring in groundwaters near central air conditioning plant site in Trombay, Maharashtra, India.

PubMed

Tirumalesh, K; Shivanna, K; Sriraman, A K; Tyagi, A K

2010-04-01

This paper summarizes the findings obtained in a monitoring study to understand the sources and processes affecting the quality of shallow and deep groundwater near central air conditioning plant site in Trombay region by making use of physicochemical and biological analyses. All the measured parameters of the groundwaters indicate that the groundwater quality is good and within permissible limits set by (Indian Bureau of Standards 1990). Shallow groundwater is dominantly of Na-HCO(3) type whereas deep groundwater is of Ca-Mg-HCO(3) type. The groundwater chemistry is mainly influenced by dissolution of minerals and base exchange processes. High total dissolved solids in shallow groundwater compared to deeper ones indicate faster circulation of groundwater in deep zone preferably through fissures and fractures whereas groundwater flow is sluggish in shallow zone. The characteristic ionic ratio values and absence of bromide point to the fact that seawater has no influence on groundwater system.

Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maggio-Price, L.; Wolf, N.S.; Priestley, G.V.

1988-09-01

Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture ofmore » anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities.« less

beta- and gamma-Comparative dose estimates on Enewetak Atoll.

PubMed

Crase, K W; Gudiksen, P H; Robison, W L

1982-05-01

Enewetak Atoll is one of the Pacific atolls used for atmospheric testing of U.S. nuclear weapons. Beta dose and gamma-ray exposure measurements were made on two islands of the Enewetak Atoll during July-August 1976 to determine the beta and low energy gamma-contribution to the total external radiation doses to the returning Marshallese. Measurements were made at numerous locations with thermoluminescent dosimeters (TLD), pressurized ionization chambers, portable NaI detectors, and thin-window pancake GM probes. Results of the TLD measurements with and without a beta-attenuator indicate that approx. 29% of the total dose rate at 1 m in air is due to beta- or low energy gamma-contribution. The contribution at any particular site, however, is somewhat dependent on ground cover, since a minimal amount of vegetation will reduce it significantly from that over bare soil, but thick stands of vegetation have little effect on any further reductions. Integral 30-yr external shallow dose estimates for future inhabitants were made and compared with external dose estimates of a previous large scale radiological survey (En73). Integral 30-yr shallow external dose estimates are 25-50% higher than whole body estimates. Due to the low penetrating ability of the beta's or low energy gamma's, however, several remedial actions can be taken to reduce the shallow dose contribution to the total external dose.

The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model.

PubMed

Nam, Hui Yin; Karunanithi, Puvanan; Loo, Wagner Cheng; Naveen, Sangeetha; Chen, Hui; Hussin, Paisal; Chan, Lucy; Kamarul, Tunku

2013-09-20

Treatment of chondral injuries remains a major issue despite the many advances made in cartilage repair techniques. Although it has been postulated that the use of marrow stimulation in combination with cell-based therapy may provide superior outcome, this has yet to be demonstrated. A pilot study was thus conducted to determine if bone marrow derived mesenchymal stromal cells (BM-MSCs) have modulatory effects on the repair outcomes of bone marrow stimulation (BMS) techniques. Two full-thickness chondral 5 mm diameter defects were created in tandem on the medial condyle of left stifle joints of 18 Boer caprine (N = 18). Goats were then divided equally into three groups. Simultaneously, bone marrow aspirates were taken from the iliac crests from the goats in Group 1 and were sent for BM-MSC isolation and expansion in vitro. Six weeks later, BMS surgery, which involves subchondral drilling at the defect sites, was performed. After two weeks, the knees in Group 1 were given autologous intra-articular BM-MSCs (N = 6). In Group 2, although BMS was performed there were no supplementations provided. In Group 3, no intervention was administered. The caprines were sacrificed after six months. Repairs were evaluated using macroscopic assessment through the International Cartilage Repair Society (ICRS) scoring, histologic grading by O'Driscoll score, biochemical assays for glycosaminoglycans (GAGs) and gene expressions for aggrecan, collagen II and Sox9. Histological and immunohistochemical analyses demonstrated hyaline-like cartilage regeneration in the transplanted sites particularly in Group 1. In contrast, tissues in Groups 2 and 3 demonstrated mainly fibrocartilage. The highest ICRS and O'Driscoll scorings was also observed in Group 1, while the lowest score was seen in Group 3. Similarly, the total GAG/total protein as well as chondrogenic gene levels were expressed in the same order, that is highest in Group 1 while the lowest in Group three. Significant differences between these 3 groups were observed (P <0.05). This study suggests that supplementing intra-articular injections of BM-MSCs following BMS knee surgery provides superior cartilage repair outcomes.

Accelerated hematopoietic recovery with angiotensin-(1-7) after total body radiation.

PubMed

Rodgers, Kathleen E; Espinoza, Theresa; Roda, Norma; Meeks, Christopher J; Hill, Colin; Louie, Stan G; Dizerega, Gere S

2012-06-01

Angiotensin (1-7) [A(1-7)] is a component of the renin angiotensin system (RAS) that stimulates hematopoietic recovery after myelosuppression. In a Phase I/IIa clinical trial, thrombocytopenia after chemotherapy was reduced by A(1-7). In this study, the ability of A(1-7) to improve recovery after total body irradiation (TBI) is shown with specific attention to radiation-induced hematopoietic injury. Mice were exposed to TBI (doses of 2-7 Gray [Gy]) of cesium 137 gamma rays, followed by treatment with A(1-7), typical doses were 100-1000 μg/kg given once or once daily for a specified number of days depending on the study. Animals are injected subcutaneously via the nape of the neck with 0.1 ml drug in saline. The recovery of blood and bone marrow cells was determined. Effects of TBI and A(1-7) on survival and bleeding time was also evaluated. Daily administration of A(1-7) after radiation exposure improved survival (from 60% to 92-97%) and reduced bleeding time at day 30 after TBI. Further, A(1-7) increased early mixed progenitors (3- to 5-fold), megakaryocyte (2- to 3-fold), myeloid (3- to 6-fold) and erythroid (2- to 5-fold) progenitors in the bone marrow and reduced radiation-induced thrombocytopenia (RIT) (up to 2-fold). Reduction in the number of treatments to 3 per week also improved bone marrow recovery and reduced RIT. As emergency responder and healthcare systems in case of nuclear accident or/and terrorist attack may be overwhelmed, the consequence of delayed initiation of treatment was ascertained. Treatment with A(1-7) can be delayed up to 5 days and still be effective in the reduction of RIT or acceleration of bone marrow recovery. The data presented in this paper indicate that A(1-7) reduces the consequences of critical radiation exposure and can be initiated well after initial exposure with maximal effects on early responding hematopoietic progenitors when treatment is initiated 2 days after exposure and 5 days after exposure for the later responding progenitors and reduced thrombocytopenia. There was some effect of A(1-7) even when given days after radiation exposure.

Regional Mapping and Resource Assessment of Shallow Gas Hydrates of Japan Sea - METI Launched 3 Years Project in 2013.

NASA Astrophysics Data System (ADS)

Matsumoto, R.

2014-12-01

Agency of Natural Resources and Energy of METI launched a 3 years shallow gas hydrate exploration project in 2013 to make a precise resource assessment of shallow gas hydrates in the eastern margin of Japan Sea and around Hokkaido. Shallow gas hydrates of Japan Sea occur in fine-grained muddy sediments of shallow subsurface of mounds and gas chimneys in the form of massive nodular to platy accumulation. Gas hydrate bearing mounds are often associated with active methane seeps, bacterial mats and carbonate concretions and pavements. Gases of gas hydrates are derived either from deep thermogenic, shallow microbial or from the mixed gases, contrasting with totally microbial deep-seated stratigraphically controlled hydrates. Shallow gas hydrates in Japan Sea have not been considered as energy resource due to its limited distribution in narrow Joetsu basin. However recently academic research surveys have demonstrated regional distribution of gas chimney and hydrate mound in a number of sedimentary basins along the eastern margin of Japan Sea. Regional mapping of gas chimney and hydrate mound by means of MBES and SBP surveys have confirmed that more than 200 gas chimneys exist in 100 km x 100 km area. ROV dives have identified dense accumulation of hydrates on the wall of half collapsed hydrate mound down to 30 mbsf. Sequential LWD and shallow coring campaign in the Summer of 2014, R/V Hakurei, which is equipped with Fugro Seacore R140 drilling rig, drilled through hydrate mounds and gas chimneys down to the BGHS (base of gas hydrate stability) level and successfully recovered massive gas hydrates bearing sediments from several horizons.

Autologous bone marrow purging with LAK cells.

PubMed

Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

1993-12-01

In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

Whole-body MR imaging, bone diffusion imaging: how and why?

PubMed

Jaramillo, Diego

2010-06-01

Whole-body MRI (W-B MRI) and diffusion-weighted imaging (DWI) are two novel techniques that greatly facilitate the evaluation of many disorders of childhood. In the musculoskeletal system, these techniques primarily aid in the evaluation of the marrow, although there is increasing interest in the study of soft-tissue abnormalities with W-B MRI and of cartilage with DWI.The normal pattern of marrow transformation affects both modalities throughout childhood. Haematopoietic marrow has a much higher signal intensity than fatty marrow on W-B MRI short tau inversion recovery (STIR) images (Darge et al. Eur J Radiol 68:289-298, 2008). Diffusion is greater in haematopoietic marrow than in fatty marrow and decreases in the skeleton with age (Jaramillo et al. Pediatr Radiol 34:S48, 2004). It is important therefore to remember that the entire skeleton is haematopoietic at birth and that there is a process of marrow transformation to fatty marrow. Marrow conversion proceeds from the fingers to the shoulders and from the toes to the hips. Within each bone, fatty marrow transformation begins in the epiphyses, and within the shaft of the long bones fatty marrow transformation begins at the diaphysis and proceeds towards the metaphyses.

Skin Mast Cell Promotion in Random Skin Flaps in Rats using Bone Marrow Mesenchymal Stem Cells and Amniotic Membrane

PubMed

Chehelcheraghi, Farzaneh; Abbaszadeh, Abolfazl; Tavafi, Magid

2018-03-06

Skin flap procedures are employed in plastic surgery, but failure can lead to necrosis of the flap. Studies have used bone marrow mesenchymal stem cells (BM-MSCs) to improve flap viability. BM-MSCs and acellular amniotic membrane (AAM) have been introduced as alternatives. The objective of this study was to evaluate the effect of BM-MSCs and AAM on mast cells of random skin flaps (RSF) in rats. RSFs (80 × 30 mm) were created on 40 rats that were randomly assigned to one of four groups, including (I) AAM, (II) BM-MSCs, (III) BM-MSCs/AAM, and (IV) saline (control). Transplantation was carried out during the procedure (zero day). Flap necrosis was observed on day 7, and skin samples were collected from the transition line of the flap to evaluate the total number and types of mast cells. The development and the total number of mast cells were related to the development of capillaries. The results of one-way ANOVA indicated that there was no statistically significant difference between the mean numbers of mast cell types for different study groups. However, the difference between the total number of mast cells in the study groups was statistically significant (p = 0.001). The present study suggests that the use of AAM/BM-MSCs can improve the total number of mast cells and accelerate the growth of capillaries at the transient site in RSFs in rats.

Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

PubMed

Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

2017-02-01

An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

PubMed

Datta, N K; Das, K P; Alam, M S; Kaiser, M S

2014-07-01

Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is <0.001. Follow up period was 6 month to 11 years. From our study it was realized that freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow is useful graft material for healing of the lesional area as well as restoring structural integrity for the treatment of unicameral bone cyst.

Changes in shallow groundwater quality beneath recently urbanized areas in the Memphis, Tennessee area

USGS Publications Warehouse

Barlow, Jeannie R.; Kingsbury, James A.; Coupe, Richard H.

2012-01-01

Memphis, the largest city in the state of Tennessee, and its surrounding suburbs depend on a confined aquifer, the Memphis aquifer, for drinking water. Concern over the potential for downward movement of water from an overlying shallow aquifer to the underlying Memphis aquifer provided impetus for monitoring groundwater quality within the shallow aquifer. The occurrence of volatile organic compounds (VOCs), nitrate, and pesticides in samples from the shallow well network indicate a widespread affect on water quality from the overlying urban land use. Total pesticide concentration was generally higher in more recently recharged groundwater indicating that as the proportion of recent water increases, the occurrence of pesticides related to the current urban land use also increases. Groundwater samples with nitrate concentrations greater than 1.5 mg/l and detectable concentrations of the pesticides atrazine and simazine also had higher concentrations of chloroform, a VOC primarily associated with urban land use, than in other samples. The age of the water from these wells indicates that these concentrations are most likely not representative of past agricultural use, but of more recent urban use of these chemicals. Given that the median age of water represented by the shallow well network was 21 years, a lag time likely exists between changes in land use and the occurrence of constituents related to urbanization in shallow groundwater.

An energy and potential enstrophy conserving scheme for the shallow water equations. [orography effects on atmospheric circulation

NASA Technical Reports Server (NTRS)

Arakawa, A.; Lamb, V. R.

1979-01-01

A three-dimensional finite difference scheme for the solution of the shallow water momentum equations which accounts for the conservation of potential enstrophy in the flow of a homogeneous incompressible shallow atmosphere over steep topography as well as for total energy conservation is presented. The scheme is derived to be consistent with a reasonable scheme for potential vorticity advection in a long-term integration for a general flow with divergent mass flux. Numerical comparisons of the characteristics of the present potential enstrophy-conserving scheme with those of a scheme that conserves potential enstrophy only for purely horizontal nondivergent flow are presented which demonstrate the reduction of computational noise in the wind field with the enstrophy-conserving scheme and its convergence even in relatively coarse grids.

Lessons learned using water quality models to develop numeric nutrient criteria for a Gulf coast estuary

EPA Science Inventory

Pensacola Bay is a shallow, mesotrophic estuary located in the north-central coast of the Gulf of Mexico, US. In November 2012, the US Environmental Protection Agency (US EPA) proposed numeric total nitrogen (TN), total phosphorus (TP), and chlorophyll-a (chl-a) water quality cr...

Mercury in sediment, water, and fish in a managed tropical wetland-lake ecosystem.

PubMed

Malczyk, Evan A; Branfireun, Brian A

2015-08-15

Mercury pollution has not been well documented in the inland lakes or fishes of Mexico, despite the importance of freshwater fish as a source of protein in local diets. Total mercury and methylmercury in waters, sediments, and the commercial fish catch were investigated in Lake Zapotlán, Mexico. Concentrations of total and methylmercury were very high in runoff and wastewater inputs, but very low in sediments and surface waters of the open water area of the lake. Concentrations of total mercury in tilapia and carp were very low, consistent with the low concentrations in lake water and sediments. Particle settling, sorption, the biogeochemical environment, and/or bloom dilution are all plausible explanations for the significant reductions in both total mercury and methylmercury. Despite very high loading of mercury, this shallow tropical lake was not a mercury-impaired ecosystem, and these findings may translate across other shallow, alkaline tropical lakes. Importantly, the ecosystem services that seemed to be provided by peripheral wetlands in reducing mercury inputs highlight the potential for wetland conservation or restoration in Mexico. Copyright © 2015. Published by Elsevier B.V.

Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment

PubMed Central

Liang, Fan; Wamala, Isaac; Scalea, Joseph; Tena, Aseda; Cormack, Taylor; Pratts, Shannon; Struuck, Raimon Duran; Elias, Nahel; Hertl, Martin; Huang, Christene A.; Sachs, David H.

2013-01-01

Background The development of genetically modified pigs which lack the expression of alpha 1–3 galactosyl transferase, (GalT-KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre-existing antibodies against the Gal epitope. However, antibodies against other antigens (anti-non-Gal antibodies), are found at varying levels in the pre-transplant sera of most primates. We have previously found that baboons with high levels of pre-transplant anti-non-Gal IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft following pig-to-baboon bone marrow transplantation [8]. Two baboons with low levels of pre-transplant anti-non-Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28 days following transplantation, suggesting engraftment. These baboons also showed evidence of donor-specific hypo-responsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre-transplant anti-non-Gal IgG levels might improve engraftment levels following GalT-KO pig-to-baboon bone marrow transplantation. Methods Five baboons, with low pre-transplant anti-non-Gal IgG levels, received transplantation of bone marrow cells (1–5 × 10^9/kg of recipient weight) from GalT-KO pigs. They received a non-myeloablative conditioning regimen consisting of low-dose total body irradiation (150cGy), thymic irradiation (700cGy), anti-thymocyte globulin (ATG) and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra-corporeal immunoadsorption using GalT-KO pig livers. Bone marrow engraftment was assessed by porcine-specific PCR on colony forming units (CFU) of day 28 bone marrow aspirates. Anti-non-Gal antibody levels were assessed by serum binding towards GalT-KO PBMC using flow cytometry (FACS). Peripheral macro-chimerism was measured by FACS using pig and baboon-specific antibodies and baboon anti-pig cellular responses were assessed by mixed lymphocyte reactions (MLR). Results As previously reported, two of five baboons demonstrated detectable bone marrow engraftment at four weeks after transplantation. Engraftment was associated with lack of an increase in anti–non-Gal IgG levels as well as cellular hypo-responsiveness towards pig. Three subsequent baboons with similarly low levels of pre-existing anti-non-Gal IgG showed no engraftment and an increase in anti-non-Gal IgG antibody levels following transplantation. Peripheral macrochimerism was only seen for a few days following transplantation regardless of antibody development. Conclusions Selecting for baboon recipients with low levels of pre-transplant anti-non-Gal IgG did not ensure bone marrow engraftment. Failure to engraft was associated with an increase in anti-non-Gal IgG levels following transplantation. These results suggest that anti-non-Gal-IgG is likely involved in early bone marrow rejection and that successful strategies for combating anti-non-Gal IgG development may allow better engraftment. Since engraftment was only low and transient regardless of antibody development, innate immune, or species compatibility mechanisms will likely also need to be addressed in order to achieve long term engraftment. PMID:24289469

Dissecting the variable source area concept - Flow paths and water mixing processes

NASA Astrophysics Data System (ADS)

Dahlke, H. E.; Easton, Z. M.; Lyon, S. W.; Brown, L. D.; Walter, M. T.; Steenhuis, T.

2010-12-01

Variable source areas (VSAs) are hot spots of hydrological (saturation excess runoff) and biogeochemical processes (e.g. nitrogen, phosphorus, organic carbon cycling) in the landscapes of the northeastern U.S. The prevalence of shallow, highly transmissive soils, steep topography, and impeding layers in the soil (i.e. fragipan) have long been recognized as first-order controls on VSA formation. Nevertheless, there is still understanding to be gained by studying subsurface flow processes in VSAs. Thus, we instrumented (trenched) a 0.5 ha hillslope in the southern tier of New York State, U.S.A. and measured water fluxes in the trench, upslope water table dynamics, surface and bedrock topography in conjunction with isotopic and geochemical tracers in order to four-dimensionally characterize (XYZ and Time) subsurface storm flow response within the VSA for five storm events. We used tracer-based hydrograph separation models and physically measured flow components to separate temporally (i.e. event and pre-event) and spatially shallow water from above the fragipan layer (including both surface runoff and shallow interflow) and deeper water from below the fragipan layer. Shallow water (event/pre-event) contributions were greatest during storms with wet antecedent conditions and large rainfall amounts (> 15 mm), when soils above the fragipan were saturated, prohibiting deep percolation through cracks in the fragipan. Shallow water contributions were well correlated to the saturated contributing area. During these events, the pre-event shallow water peaked on the rising and falling limb, which can be explained by flushing of pre-event water from macropores on the rising limb and subsequent drainage of pre-event water from micropores into macropores on the falling limb. During events with dry antecedent conditions, greater amounts of event water (24 - 28 %) are proportionally contributed by surface runoff in the top 10 cm of the soil through macropores than by shallow interflow from the soil-fragipan interface. Pre-event deeper water contributions to total trench discharge varied between 15 and 65% but were independent of total rainfall amounts, rainfall intensities, and water table dynamics. Our results have important implication for the protection of streams from dissolved pollutant transport and recommend that preference be given to variable-width buffers over fixed-width stream buffers.

[Bone marrow autotransplantation in patients with acute myeloblastic leukemia in primary remission].

PubMed

Richard, C; Iriondo, A; Baro, J; Conde, E; Hermosa, V; Alsar, M J; Gómez Casares, M T; Muruzabal, M J; Pérez Encinas, M; Zubizarreta, A

1990-09-22

Fifteen bone marrow autotransplants (BMAT) in patients with acute myeloblastic leukemia (AML) were performed after the first remission. The mean age was 37 years (range 12 to 60 years). According to the morphological classification FAB, 8 patients had monocytic leukemia (M4, M5) and 7 myeloid leukemia (M1, M2, M3). The mean interval elapsed between the date of complete remission and the BMAT was 3.9 months (range 1 to 5-9 months). In 8 patients this interval was longer than 6 months and in 7 cases it was shorter than 6 months. After achievement of the complete remission all patients underwent certain cycles of intensification before the BMAT. Eight patients received only a cycle whereas 7 patients received more than one cycle (between 2 and 4). The conditioning protocol consisted of cyclophosphamide (CP) (60 mg/kg x 2) and total body radiotherapy (TBR) (10 Gy) in 9 patients; CP and busulfan in five; and CP, cytarabine at high doses and melphalan in one case. Marrow extraction was performed after completion of chemotherapy of intensification. In 5 cases the bone marrow was depleted of leukemic cells by previous in vitro treatment with ASTA-Z. There are at present 8 alive patients. The survival free of illness was 51.8%. Seven patients died: 3 cases because relapse of the leukemia, 3 due to attachment failure of the transplantation, and one patient suffered a viral myocarditis. The survival free of illness was significantly longer in those patients transplanted after 6 months of the complete remission.

Marrow donor registry and cord blood bank in Taiwan.

PubMed

Lee, Tsung Dao

2002-08-01

Unrelated Bone marrow transplant was initiated thirty years ago. Though there are over millions of donors registered with the bone marrow registries worldwide, Asian patients rarely find a match with all these donors. Tzu Chi Marrow Donor Registry was established to meet this need. It has become the largest Asian marrow donor registry in the world. With the introduction of high technology to test the HLA of the donors and recipients, the success rate of bone marrow transplant is greatly improved among Asian countries. 50% of blood disease Asian patients who cannot find a bone marrow matched donor will be complemented by the establishment of cord blood banks in Taiwan.

Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry

PubMed Central

Al-Quran, Samer Z.; Yang, Lijun; Magill, James M.; Braylan, Raul C.; Douglas-Nikitin, Vonda K.

2012-01-01

Summary Assessment of bone marrow involvement by malignant plasma cells is an important element in the diagnosis and follow-up of patients with multiple myeloma and other plasma cell dyscrasias. Microscope-based differential counts of bone marrow aspirates are used as the primary method to evaluate bone marrow plasma cell percentages. However, multiple myeloma is often a focal process, a fact that impacts the accuracy and reliability of the results of bone marrow plasma cell percentages obtained by differential counts of bone marrow aspirate smears. Moreover, the interobserver and intraobserver reproducibility of counting bone marrow plasma cells microscopically has not been adequately tested. CD138 allows excellent assessment of plasma cell numbers and distribution in bone marrow biopsies. We compared estimates of plasma cell percentages in bone marrow aspirates and in hematoxylin-eosin– and CD138-stained bone marrow biopsy sections (CD138 sections) in 79 bone marrows from patients with multiple myeloma. There was a notable discrepancy in bone marrow plasma cell percentages using the different methods of observation. In particular, there was a relatively poor concordance of plasma cell percentage estimation between aspirate smears and CD138 sections. Estimates of plasma cell percentage using CD138 sections demonstrated the highest interobserver concordance. This observation was supported by computer-assisted image analysis. In addition, CD138 expression highlighted patterns of plasma cell infiltration indicative of neoplasia even in the absence of plasmacytosis. We conclude that examination of CD138 sections should be considered for routine use in the estimation of plasma cell load in the bone marrow. PMID:17714757

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging.

PubMed

Rahmouni, Alain; Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Belhadj, Karim; Gaulard, Philippe; Bouanane, Mohamed; Golli, Mondher; Kobeiter, Hicham

2003-12-01

To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

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

Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

PubMed

Afshar, Solmaz F; Zawaski, Janice A; Inoue, Taeko; Rendon, David A; Zieske, Arthur W; Punia, Jyotinder N; Sabek, Omaima M; Gaber, M Waleed

2017-07-01

The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T 2 -weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

The effect of hydrostatic pressure on staurosporine-induced neural differentiation in mouse bone marrow‑derived mesenchymal stem cells.

PubMed

Javanmard, F; Azadbakht, M; Pourmoradi, M

2016-01-01

In this study, the role of hydrostatic pressure on staurosporine-induced neural differentiation in mouse bone marrow mesenchymal stem cells were investigated. The cells were cultured in treatment medium containing 100 nM of staurosporine for 4 hours; then the cells were affected by hydrostatic pressure (0, 25,50, 100 mmHg). The percentage of cell viability by trypan blue staining and the percentage of cell death by Hoechst/PI differential staining were assessed. We obtained the total neurite length. Expression of β-tubulin III and GFAP (Glial fibrillary acidic protein) proteins were also analyzed by immunocytochemistry. The percentage of cell viability in treatments decreased relative to the increase in hydrostatic pressure and time (p Keywords: bone marrow mesenchymal stem cell, hydrostatic pressure, immunocytochemistry, neural differentiation, neurite length, cell differentiation.

Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

PubMed Central

Chou, Wen-Hai; Choi, Doo-Sup; Zhang, Hong; Mu, Dezhi; McMahon, Tom; Kharazia, Viktor N.; Lowell, Clifford A.; Ferriero, Donna M.; Messing, Robert O.

2004-01-01

Thrombolysis is widely used to intervene in acute ischemic stroke, but reestablishment of circulation may paradoxically initiate a reperfusion injury. Here we describe studies with mice lacking protein kinase Cδ (PKCδ) showing that absence of this enzyme markedly reduces reperfusion injury following transient ischemia. This was associated with reduced infiltration of peripheral blood neutrophils into infarcted tissue and with impaired neutrophil adhesion, migration, respiratory burst, and degranulation in vitro. Total body irradiation followed by transplantation with bone marrow from PKCδ-null mice donors reduced infarct size and improved neurological outcome in WT mice, whereas marrow transplantation from WT donors increased infarction and worsened neurological scores in PKCδ-null mice. These results indicate an important role for neutrophil PKCδ in reperfusion injury and strongly suggest that PKCδ inhibitors could prove useful in the treatment of stroke. PMID:15232611

Temperature and depth mediate resource competition and apparent competition between Mysis diluviana and kokanee

USGS Publications Warehouse

Schoen, Erik R.; Beauchamp, David A.; Buettner, Anna R.; Overman, Nathanael C.

2015-01-01

In many food webs, species in similar trophic positions can interact either by competing for resources or boosting shared predators (apparent competition), but little is known about how the relative strengths of these interactions vary across environmental gradients. Introduced Mysis diluviana shrimp interact with planktivorous fishes such as kokanee salmon (lacustrine Oncorhynchus nerka) through both of these pathways, and effective management depends on understanding which interaction is more limiting under different conditions. An “environmental matching” hypothesis predicts the ecological impacts of Mysis are maximized under cool conditions near its thermal optimum. In addition, we hypothesized Mysis is more vulnerable to predation by lake trout in relatively shallow waters, and therefore Mysis enhances lake trout density and limits kokanee through apparent competition more strongly in shallower habitats. We tested whether these hypotheses could explain food web differences between two connected lake basins, one relatively shallow and the other extremely deep. The shallower basin warmed faster, thermally excluded Mysis from surface waters for 75% longer, and supported 2.5–18 times greater seasonal production of cladoceran zooplankton than the deeper basin, standardized by surface area. Mysis consumed 14–22% less zooplankton in the shallower basin, and lower ratios of total planktivore consumption to zooplankton production (C:P) indicated less potential for resource competition with kokanee, consistent with environmental matching. Lake trout diets contained more Mysis in the shallower basin and at shallower sampling sites within both basins. The catch rate of lake trout was seven times greater and the predation risk for kokanee was 4–5 times greater in the shallower basin than in the deeper basin, consistent with stronger apparent competition in shallower habitats. Understanding how the strengths of these interactions are mediated by temperature and depth would enable managers to select appropriate strategies to address the unique combinations of conditions in hundreds of affected systems.

Cyclic thermal behavior associated to the degassing process at El Hierro submarine volcano, Canary Islands.

NASA Astrophysics Data System (ADS)

Fraile-Nuez, E.; Santana-Casiano, J. M.; González-Dávila, M.

2016-12-01

One year after the ceasing of magmatic activity in the shallow submarine volcano of the island of El Hierro, significant physical-chemical anomalies produced by the degassing process as: (i) thermal anomalies increase of +0.44 °C, (ii) pH decrease of -0.034 units, (iii) total dissolved inorganic carbon, CT increase by +43.5 µmol kg-1 and (iv) total alkalinity, AT by +12.81 µmol kg-1 were still present in the area. These evidences highlight the potential role of the shallow degassing processes as a natural ecosystem-scale experiments for the study of significant effects of global change stressors on marine environments. Additionally, thermal time series obtained from a temporal yo-yo CTD study, in isopycnal components, over one of the most active points of the submarine volcano have been analyzed in order to investigate the behavior of the system. Signal processing of the thermal time series highlights a strong cyclic temperature period of 125-150 min at 99.9% confidence, due to characteristic time-scales revealed in the periodogram. These long cycles might reflect dynamics occurring within the shallow magma supply system below the island of El Hierro.

Risk of diarrhoea from shallow groundwater contaminated with enteropathogens in the Kathmandu Valley, Nepal.

PubMed

Shrestha, Sadhana; Haramoto, Eiji; Malla, Rabin; Nishida, Kei

2015-03-01

Shallow groundwater is the main water source among many alternatives in the Kathmandu Valley, Nepal, which has a rapidly growing population and intermittent piped water supply. Although human pathogens are detected in groundwater, its health effects are unclear. We estimated risk of diarrhoea from shallow groundwater use using quantitative microbial risk assessment. Escherichia coli, Giardia cyst and Cryptosporidium oocyst levels were analysed in dug and tube wells samples. E. coli concentrations were converted to those of enteropathogenic E. coli (EPEC). Risks from EPEC in dug wells and from Cryptosporidium and Giardia in both dug and tube wells were higher than the acceptable limit (<10⁻⁴ infections/person-year) for both drinking and bathing exposures. Risk from protozoan enteropathogens increased the total risk 10,000 times, indicating that ignoring protozoans could lead to serious risk underestimation. Bathing exposure considerably increased risk, indicating that it is an important pathway. Point-of-use (POU) water treatment decreased the risk six-fold and decreased risk overestimation. Because removal efficiency of POU water treatment has the largest impact on total risk, increasing the coverage and efficiency of POU water treatment could be a practical risk management strategy in the Kathmandu Valley and similar settings.

A first application of marine-controlled source method on gas-hydrate study off SW Taiwan

NASA Astrophysics Data System (ADS)

Chiang, C.; Hsu, S.; Chen, C.; Evans, R. L.

2011-12-01

Bottom simulating reflector (BSR), high methane flux, shallow sulfide/methane interface, fluid gushed from the seafloor, self-carbonate within sediment, methane reef, and self-biome are widely distributed in the offshore of the southwestern Taiwan. These geophysical and geochemistry signatures imply a high gas hydrate reservoir area. However, the upper bound of the gas hydrate and shallow section of the sediment are still unclear. This study shows the results of our first marine controlled-source electromagnetic survey in 2010 and provides the information of shallow sediment around the offshore of southwestern Taiwan. Three target areas were conducted: the southeast of Small Ryukyu Islands (seepage, G96), west of Yung-An Ridge (YAR) and northwest of Good Weather Ridge (GWR). In total, fourteen survey lines have been carried out, and the total survey length is about 72 km. Our preliminary result shows that the resistivity/porosity anomalies within pockmarks and seepages correspond to the features from the sub-bottom profilers. The range of porosity change is 4 % in G96 and YAR sites, while in the GWR site there is up to 8 % of porosity change and implies a high gas hydrate potential area.

The causes and consequences of algal blooms: the Cladophora glomerata bloom and the Neva Estuary (eastern Baltic Sea).

PubMed

Gubelit, Yulia I; Berezina, Nadezhda A

2010-01-01

The biomass dynamics of the green alga Cladophora glomerata was studied in the shallow-water littoral zone of the Neva estuary during May-October of 2003-2005. Additionally, the average production rate of C. glomerata, the biomass of drifting algae and oxygen depletion were examined during period of algae decomposition. Two peaks in C. glomerata biomass, in July and in September, were observed during all years studied, reaching a maximum 300+/-100 g DW m(-2). The primary production of C. glomerata varied from 3.6 to 7.9 g C m(-2) contributing to around 90% of the total primary production in this habitat. From the middle of July to late August the biomass of drifting C. glomerata exceeded the biomass of the attached algae, accounting for 62% of the total algal biomass in shallow areas (0-1m). The hypoxia (a minimum oxygen level of 5% or 0.62 mg dm(-3)) in the water was recorded near shore (to 20-m distance from the shore), negatively influencing the quality of shallow-water habitats. Copyright 2010 Elsevier Ltd. All rights reserved.

Notable increases in nutrient concentrations in a shallow lake during seasonal ice growth.

PubMed

Fang, Yang; Changyou, Li; Leppäranta, Matti; Xiaonghong, Shi; Shengnan, Zhao; Chengfu, Zhang

2016-12-01

Nutrients may be eliminated from ice when liquid water is freezing, resulting in enhanced concentrations in the unfrozen water. The nutrients diluted from the ice may contribute to accumulated concentrations in sediment during winter and an increased risk of algae blooms during the following spring and summer. The objective of this study was to evaluate the influence of ice cover on nitrogen (N) and phosphorus (P) concentrations in the water and sediment of a shallow lake, through an examination of Ulansuhai Lake, northern China, from the period of open water to ice season in 2011-2013. The N and P concentrations were between two and five times higher, and between two and eight times higher, than in unfrozen lakes, respectively. As the ice thickness grew, contents of total N and total P showed C-shaped profiles in the ice, and were lower in the middle layer and higher in the bottom and surface layers. Most of the nutrients were released from the ice to liquid water. The results confirm that ice can cause the nutrient concentrations in water and sediment during winter to increase dramatically, thereby significantly impacting on processes in the water environment of shallow lakes.

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

PubMed

Singh, Lakshman; Tyagi, Sonia; Myers, Damian; Duque, Gustavo

2018-04-01

Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 07: Transitioning from extended-distance total body irradiation to optimized VMAT total marrow irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherpak, Amanda; Chytyk-Praznik, Krista; Yewondwos

2016-08-15

Purpose: TMI targets only the bone marrow, with the intent of sparing normal tissues. The NSCC has recently implemented a TMI protocol which includes VMAT fields to treat the bone marrow from head to mid-thigh and extended SSD POP fields to treat the lower legs. This work describes the commissioning and initial clinical results of the first reported VMAT TMI treatments in Canada. Methods: Detailed CT simulation, imaging, planning and treatment procedures were developed by a multi-disciplinary team. Patients have 1 cm of bolus over the lower legs and 0.5 cm of bolus around the lower arms. The PTV includesmore » all bone, except mandible, facial bones and hands, with the objective of V(12 Gy) > 90%. Detailed analysis of the influence of field overlap was performed to determine optimal field placement and image-guidance tolerances. Results: PTV coverage was achieved for all cases as V(12 Gy) ranged from 90.4–96.3%. The minimum dose to the PTV, D(99%), ranged from 91.4–97.87% and V(90%Rx=10.8 Gy) ranged from 99.1–100.0%. The lungs, liver and heart had an average D{sub mean} of (7.8±0.3)Gy/(65±2)%, (7.6±0.7)Gy/(63±5)%, and (6.8±0.4)Gy/(56±4)% respectively. Conclusions: Commissioning required input and collaboration from all team members. Transitioning from TBI to TMI requires additional time for contouring, treatment planning, QA, and treatment. Patient benefit can however be seen in the quality of OAR sparing.« less

Human parvovirus B19, varicella zoster virus, and human herpesvirus-6 in mesenchymal stem cells of patients with osteoarthritis: analysis with quantitative real-time polymerase chain reaction.

PubMed

Rollín, R; Alvarez-Lafuente, R; Marco, F; Jover, J A; Hernández-García, C; Rodríguez-Navas, C; López-Durán, L; Fernández-Gutiérrez, B

2007-04-01

To investigate whether there is a possible viral transmission using mesenchymal stem cells (MSCs) in autologous or allogeneic transplantation in the context of osteoarthritis (OA) patients. The presence of parvovirus B19 (B19), varicella zoster virus (VZV), and human herpesvirus-6 (HHV-6) was studied in MSCs from bone marrow of patients with OA and healthy controls. MSCs were prepared from bone marrow aspirates obtained from 18 patients undergoing joint replacement as a result of OA and from 10 healthy controls. DNA was extracted from primary MSCs' culture established from these cells and quantitative real-time polymerase chain reaction was performed to analyse the prevalence and viral load of B19, VZV and HHV-6. The prevalence of total viral DNA among patients with OA was 16.7% (3/18), with a mean viral load of 29.7 copies/microg of DNA. One out of 18 was positive for B19 (viral load, 61.2 copies/microg of DNA), two for VZV (mean viral load, 14.4 copies/microg of DNA), and none for HHV-6. The prevalence of total viral DNA in the control group was 20% (2/10), with a mean viral load of 13.4 copies/microg of DNA. Both positive results were of B19 parvoviruses. There were no statistically significant differences among patients and controls. This first approach to the viral prevalence in MSCs of bone marrow in OA patients and healthy controls seems to show a very low risk of viral transmission or reactivation in a possible MSCs' transplantation.

Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum.

PubMed

Barba, Pere; Burns, Linda J; Litzow, Mark R; Juckett, Mark B; Komanduri, Krishna V; Lee, Stephanie J; Devlin, Sean M; Costa, Luciano J; Khan, Shakila; King, Andrea; Klein, Andreas; Krishnan, Amrita; Malone, Adriana; Mir, Muhammad; Moravec, Carina; Selby, George; Roy, Vivek; Cochran, Melissa; Stricherz, Melisa K; Westmoreland, Michael D; Perales, Miguel-Angel; Wood, William A

2016-03-01

The American Society for Blood and Marrow Transplantation (ASBMT) Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data of cases posted in the CCF from January 29, 2014 to March 18, 2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) were autologous HCT, and in 16 (12%), the type of transplantation (autologous versus allogeneic) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (n = 23, 17%), and multiple myeloma (MM; n = 20, 15%). When compared with the US transplantation activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were over-represented in the CCF, whereas MM was under-represented (P < .001). A total of 259 topics were addressed in the CCF with a median of 2 topics/case (range, 1 to 6). Particularly common topics included whether transplantation was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain.

PubMed

Bosy-Westphal, Anja; Later, Wiebke; Schautz, Britta; Lagerpusch, Merit; Goele, Kristin; Heller, Martin; Glüer, Claus-C; Müller, Manfred J

2011-07-01

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.

Blood and Bone Marrow Donation

MedlinePlus

... who's waiting for a stem cell transplant. Risks Bone marrow donation The most serious risk associated with ... or her health insurance. What you can expect Bone marrow donation Collecting stem cells from bone marrow ...

Hydrogeologic framework and simulation of ground-water flow and travel time in the shallow aquifer system in the area of Naval Support Activity Memphis, Millington, Tennessee

USGS Publications Warehouse

Robinson, James L.; Carmichael, John K.; Halford, Keith J.; Ladd, David E.

1997-01-01

Naval Support Activity (NSA) Memphis is a Department of the Navy facility located at the City of Millington, Tennessee, about 5 miles north of Memphis. Contaminants have been detected in surface-water, sediment, and ground-water samples collected at the facility. As part of the Installation Restoration Program, the Navy is considering remedial-action options to prevent or lessen the effect of ground-water contamination at the facility and to control the movement and discharge of contaminants. A numerical model of the ground-water-flow system in the area of NSA Memphis was constructed and calibrated so that quantifiable estimates could be made of ground-water-flow rates, direction, and time-of-travel. The sediments beneath NSA Memphis, to a depth of about 200 feet, form a shallow aquifer system. From youngest to oldest, the stratigraphic units that form the shallow aquifer system are alluvium, loess, fluvial deposits, and the Cockfield and Cook Mountain Formations. The shallow aquifer system is organized into five hydrogeologic units: (1) a confining unit composed of the relatively low permeability sediments of the upper alluvium and the loess; (2) the A1 aquifer comprising sand and gravel of the lower alluvium and the fluvial deposits, and sand lenses in the upper part of the preserved section of the Cockfield Formation; (3) a confining unit composed of clay and silt within the upper part of the Cockfield Formation; (4) the Cockfield aquifer comprising sand lenses within the lower part of the preserved section of the Cockfield Formation; and (5) a confining unit formed by low permeability sediments of the Cook Mountain Formation that composes the upper confining unit for the Memphis aquifer. Thicknesses of individual units vary considerably across the facility. Structural and depositional features that affect the occurrence of ground water in the shallow aquifer system include faulting, an erosional scarp, and 'windows' in the confining units. Underlying the shallow aquifer system is the Memphis aquifer, the primary source of water for NSA Memphis and the City of Memphis, Tennessee. Analyses of sediment cores, aquifer and well specific-capacity tests, and numerical modeling were used to estimate the hydraulic characteristics of units of the shallow aquifer system. The vertical hydraulic conductivity of core samples of the alluvium-loess confining unit ranged from about 8.5 x 10-5 to 1.6 x 10-2 feet per day, and the total porosity of the samples ranged from about 35 to 48 percent. The results of the aquifer test were used to estimate a horizontal hydraulic conductivity of about 5 feet per day for the alluvial-fluvial deposits aquifer. The total porosity of core samples of the alluvial-fluvial deposits aquifer ranged from about 22 to 39 percent. The vertical hydraulic conductivity of core samples of the Cockfield confining unit ranged from about 4.5 x 10-5 to 2.5 x 10-3 feet per day, and the total porosity ranged from about 41 to 55 percent. Well specific-capacity tests indicate that the horizontal hydraulic conductivity of sand units that compose the Cockfield aquifer range from about 0.5 to 3 feet per day. The vertical hydraulic conductivity of core samples of the Cook Mountain confining unit ranged from about 5.0 x 10-6 to 9.9 x 10-4 feet per day. Total porosity of core samples of the Cook Mountain confining unit ranged from about 30 to 42 percent. Ground-water flow and time-of-travel in the shallow aquifer system were simulated using the MODFLOW finite-difference model and the -particle-tracking program MODPATH. A three-layer, steady-state model of the shallow aquifer system was constructed and calibrated to the potentiometric surface of the A1 aquifer. Results of numerical modeling support the proposed conceptual hydrogeologic model of the shallow aquifer system. Ground-water time-of-travel in the A1 aquifer was simulated using an assumed effective porosity of 25 percent. Typical ground-water-flow velocities were on the or

Quality-assurance data, comparison to water-quality standards, and site considerations for total dissolved gas and water temperature, lower Columbia River, Oregon and Washington, 2001

USGS Publications Warehouse

Tanner, Dwight Q.; Bragg, Heather M.

2002-03-06

At times in July and August 2001, the total-dissolved-gas probe at Warrendale could not be positioned below the minimum compensation depth because the river was too shallow at that location. Consequently, degassing at probe depth may have occurred, and total dissolved gas may have been larger in locations with greater depths.

Quality of Ground Water in Shallow Wells in Agricultural Areas of Haywood, Shelby, Lake, and Obion Counties, Tennessee, January and February 1988

DTIC Science & Technology

1988-01-01

total of 20 wells will be sampled for this study; 7 wells in Haywood County, 6 wells in Lake County near Reelfoot Lake and one in Obion County, and 6...1985, May 1984-April 1985 water budget of Reelfoot Lake with estimates of sediment inflow and concentrations of pesticides in bottom material in...i i . QUALITY OJ? GROUND WATER IN SHALLOW WELLS IN AGRICULTURAL AREAS OF HAYWOOD, SHELBY, LAKE , AND OBION COUNTIES, TENNESSEE, JANUARY

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

Bone Marrow Test: MedlinePlus Lab Test Information

MedlinePlus

... this page: https://medlineplus.gov/labtests/bonemarrowtest.html Bone Marrow Test To use the sharing features on this page, please enable JavaScript. What Are Bone Marrow Tests? Bone marrow is a soft, spongy ...

Interactions between deep bedrock aquifers and surface water in function of recharge and topography: a numerical study

NASA Astrophysics Data System (ADS)

Goderniaux, P.; Davy, P.; Le Borgne, T.; Bresciani, E.; Jimenez-Martinez, J.

2011-12-01

In crystalline rock regions, such as Brittany (France), important reserves of groundwater into deep fractured aquifers are increasingly used and provide high quality water compared to shallow aquifers which can be subject to agricultural contamination. However, recharge processes of these deep aquifers and interactions with surface water are not yet fully understood. In some areas, intensive pumping is carried out without guarantee of the resource quantity and quality. Understanding these processes is crucial for sustainable management of the resource. In this study, we study how deep groundwater fluxes, pathways, ages, and river-aquifer interactions vary according to recharge. We assume that water flowing from the ground surface is distributed between shallow more permeable layers and deep layers. This repartition mostly depends on recharge rates. With high recharge, groundwater levels are high and subsurface streamlines are relatively short between recharge areas and existing draining rivers, which constitutes a very dense network. Therefore, most of the groundwater fluxes occur through the more permeable shallow layers. With low recharge, groundwater levels are lower, and river and shallow permeable levels are partly disconnected from each other. This induces a general increase of the groundwater streamlines length from the recharge areas to more sporadic discharge areas, and more fluxes occur through the deep layers. Recharge conditions and river-aquifer interactions have changed over the last thousands of years, due to change in precipitation, temperatures, existence of permafrost, etc. They have strongly influenced deep groundwater fluxes and can explain current groundwater age and flux distribution. To study these interactions, a regional-scale finite difference flow model was implemented. The model covers an area of 1400 km 2 , a depth of 1 km, and the topography is characteristic of Brittany. As rivers are mainly fed by groundwater drainage, seepages faces are used on the whole modelled area, so that the river network is not prescribed but dependent on simulated groundwater conditions. Different recharge conditions were tested (from 20 to 500 mm/yr). Results show that streamline lengths and groundwater ages have exponential distributions with characteristic lengths increasing with decreasing recharge. The total area of discharge zones decreases with recharge. Groundwater age is quite variable and increases with depth, but the variability is much more important in discharge areas than recharge areas. The proportion of groundwater discharge into the sea (compared to total recharge) increases when total recharge decreases. The model was also used to test the influence of heterogeneity or hydraulic conductivity contrast between shallow and deep layers on deep groundwater fluxes. In a completely homogeneous model, deep fluxes are correlated with recharge fluxes. Correlation decreases while contrast increases. If the permeability of the shallow weather zone is now 3 orders of magnitude larger than of deep aquifer, we observed that simulated deep groundwater fluxes increase locally, despite total recharge at the level of the ground surface decreases.

Niche recycling through division-independent egress of hematopoietic stem cells

PubMed Central

Czechowicz, Agnieszka; Ooi, A.G. Lisa; Rossi, Derrick J.; Bryder, David; Weissman, Irving L.

2009-01-01

Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that ∼1–5% of the total pool of HSCs enters into the circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. Consistent with this, repetitive daily transplantations of small numbers of HSCs administered as new niches became available over the course of 7 d led to significantly higher levels of engraftment than did large, single-bolus transplantations of the same total number of HSCs. These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress. PMID:19887396

Relative importance of the bone marrow and spleen in the production and dissemination of B lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosse, C.; Cole, S.B.; Appleton, C.

1978-04-01

The relative importance of the bone marrow and spleen in the production of B lymphocytes was investigated in guinea pigs by the combined use of (/sup 3/H)TdR radioautography and fluorescent microscopy after the staining of B cells by FITC-F (ab')/sub 2/-goat-anti-guinea pig Ig. Large and small lymphoid cells possess sIg in the marrow and spleen but B cell turnover in the marrow exceeds that in the spleen. That newly generated bone marrow B cells are not derived from an extramyeloid bursa equivalent was demonstrated by the absence of (/sup 3/H)TdR labeled B cells in tibial marrow 72 hr after (/supmore » 3/H)TdR was administered systemically, while the circulation to the hind limbs was occluded. Pulse and chase studies with (/sup 3/H)TdR showed that large marrow B cells are derived from sIg-negative, proliferating precursors resident in the bone marrow and not from the enlargement of activated small B lymphocytes. The acquisition of (/sup 3/H)TdR by splenic B cells lagged behind that observed in the marrow. Three days after topical labeling of tibial and femoral bone marrow with (/sup 3/H)TdR, a substantial proportion of splenic B cells were replaced by cells that had seeded there from the labeled marrow. The studies unequivocally identify the bone marrow as the organ of primary importance in B cell generation, and indicate that in the guinea pig rapidly renewed B lymphocytes of the spleen are replaced by lymphocytes recently generated in bone marrow. The rate of replacement of B lymphocytes in the lymph node by cells newly generated in the bone marrow takes place at a slower tempo than in the spleen.« less

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro.

PubMed

Torisawa, Yu-suke; Spina, Catherine S; Mammoto, Tadanori; Mammoto, Akiko; Weaver, James C; Tat, Tracy; Collins, James J; Ingber, Donald E

2014-06-01

Current in vitro hematopoiesis models fail to demonstrate the cellular diversity and complex functions of living bone marrow; hence, most translational studies relevant to the hematologic system are conducted in live animals. Here we describe a method for fabricating 'bone marrow-on-a-chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device. The engineered bone marrow (eBM) retains hematopoietic stem and progenitor cells in normal in vivo-like proportions for at least 1 week in culture. eBM models organ-level marrow toxicity responses and protective effects of radiation countermeasure drugs, whereas conventional bone marrow culture methods do not. This biomimetic microdevice offers a new approach for analysis of drug responses and toxicities in bone marrow as well as for study of hematopoiesis and hematologic diseases in vitro.

Changes in compartments of hemospoietic and stromal marrow progenitor cells after continuous low dose gamma-irradiation

NASA Astrophysics Data System (ADS)

Domaratskaya, E.; Starostin, V.

The low dose continuous gamma-irradiation chosen corresponded with that affected the organisms onboard a spacecraft (Mitrikas, Tsetlin, 2000). F1 (CBAxC57Bl/6) male and female mice were used at 3 4 months of age. Experimental mice were- irradiated during 10 days to a total dose of 15 mGy (Co60 gamma-sources, mean dose rate of 1.5-2.0 mGy/day). Another group of intact mice served as control. Younger and advanced hemopoietic progenitors measured at day 11 (i.e. CFU -S-11) and day 7 (i.e. CFU-S-7), respectively, after transplantation of test donor cells were assayed by the method of Till and McCulloch (1961). Stromal changes were evaluated by estimation of in vitro fibroblastic colony-forming units (CFU -F ) content and by the ability of ectopically grafted (under renal capsule) stroma to regenerate the new bone marrow organ. CFU-S-11 number increased of 40% as compared with control and almost 2-fold higher than that of CFU-S-7. The CFU-F content increased almost of 3-fold. Size of ectopic marrow transplants was estimated at day 70 following grafting by counting myelokariocyte and CFU -S number that repopulated the newly formed bone marrow organ. It was found more than 2-fold increase of myelokariocytes in transplants produced by marrow stroma of irradiated donors. CFU -S contents in transplants increased strikingly in comparison to control level. CFU-S-7 and CFU-S-11 increased of 7.5- and of 3.7-fold, respectively, i.e. the rate of advanced CFU - S predominated. It should be noted a good correlation between number of stromal progenitor cells (CFU-F) and ectopic transplant sizes evaluated as myelokaryocyte counts when irradiated donors used. In the same time, if sizes of transplants was measured as CFU-S-7 and CFU - S-11 numbers, their increases were more pronounced. Therefore, continuous low dose gamma- irradiation augments significantly both hemopoietic and stromal progenitor cell number in bone marrow. Additionally, the ratio of distinct CFU -S subpopulations changes. Stromal cells acquire the ability to form much greater hemopoietic territories and seems to create the microenvironments of another quality with stimulatory effects on CFU - S proliferation.

Comparison of collagen matrix treatment impregnated with platelet rich plasma vs bone marrow.

PubMed

Minamimura, Ai; Ichioka, Shigeru; Sano, Hitomi; Sekiya, Naomi

2014-02-01

This study has reported the efficacy of an autologous bone marrow-impregnated collagen matrix experimentally and clinically. Then, it reflected that platelet rich plasma (PRP) was as good a source of growth factors as bone marrow and available in a less invasive procedure. This study aimed to compare the efficacy of a PRP-impregnated collagen matrix with that of a bone marrow-impregnated collagen matrix by quantifying wound size and capillary density using genetically diabetic db/db mice. Bone marrow cells were obtained from femurs of ddy mice. Then, a small amount of collagen matrix was immersed in bone marrow suspension. This is called a bone marrow-impregnated collagen matrix. PRP was obtained from healthy human blood and a small amount of collagen matrix was immersed in PRP. This is called a PRP-impregnated collagen matrix. A bone marrow-impregnated collagen matrix and PRP-impregnated collagen matrix were applied to excisional skin wounds on a genetically healing-impaired mouse (n = 6) and wounds were evaluated 6 days after the procedure. Wounds were divided into two groups: PRP (n = 6), in which a PRP-impregnated collagen matrix was applied; and bone marrow (n = 6), in which collagen immersed in a bone marrow suspension was applied. There was no significant difference between the PRP and bone-marrow groups in the rate of vascular density increase or wound size decrease. The present study suggested that the PRP-impregnated collagen matrix promotes repair processes at least as strongly as the bone marrow-impregnated collagen matrix. Given lower invasiveness, the PRP-impregnated collagen matrix would have advantages in clinical use.

Shallow Gas Migration along Hydrocarbon Wells-An Unconsidered, Anthropogenic Source of Biogenic Methane in the North Sea.

PubMed

Vielstädte, Lisa; Haeckel, Matthias; Karstens, Jens; Linke, Peter; Schmidt, Mark; Steinle, Lea; Wallmann, Klaus

2017-09-05

Shallow gas migration along hydrocarbon wells constitutes a potential methane emission pathway that currently is not recognized in any regulatory framework or greenhouse gas inventory. Recently, the first methane emission measurements at three abandoned offshore wells in the Central North Sea (CNS) were conducted showing that considerable amounts of biogenic methane originating from shallow gas accumulations in the overburden of deep reservoirs were released by the boreholes. Here, we identify numerous wells poking through shallow gas pockets in 3-D seismic data of the CNS indicating that about one-third of the wells may leak, potentially releasing a total of 3-17 kt of methane per year into the North Sea. This poses a significant contribution to the North Sea methane budget. A large fraction of this gas (∼42%) may reach the atmosphere via direct bubble transport (0-2 kt yr -1 ) and via diffusive exchange of methane dissolving in the surface mixed layer (1-5 kt yr -1 ), as indicated by numerical modeling. In the North Sea and in other hydrocarbon-prolific provinces of the world shallow gas pockets are frequently observed in the sedimentary overburden and aggregate leakages along the numerous wells drilled in those areas may be significant.

Meeting report of the 2016 bone marrow adiposity meeting.

PubMed

van der Eerden, Bram; van Wijnen, André

2017-10-02

There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies.

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

PubMed

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without BM invasion showing high level of bone marrow plasma vascular endothelial growth factor per platelet count had significantly shorter progression-free survival and overall survival. Bone marrow plasma vascular endothelial growth factor level per platelet count might be associated with bone marrow invasion by diffuse large B-cell lymphoma and is correlated with clinical outcomes after treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed Central

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

2014-01-01

Background The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. Methods Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 µg/mL, 100 µg/mL) or Ginsenoside Rg1 (100 µg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. Results The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6×107 and 1.3-48×107 and 8.9×104 and 1.8-80×104, respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. Conclusion Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage. PMID:25325037

Italian Multicenter Study on Accuracy of 18F-FDG PET/CT in Assessing Bone Marrow Involvement in Pediatric Hodgkin Lymphoma.

PubMed

Cistaro, Angelina; Cassalia, Laura; Ferrara, Cinzia; Quartuccio, Natale; Evangelista, Laura; Bianchi, Maurizio; Fagioli, Franca; Bisi, Gianni; Baldari, Sergio; Zanella, Alessandro; Pillon, Marta; Zucchetta, Pietro; Burei, Marta; Sala, Alessandra; Guerra, Luca; Guglielmo, Priscilla; Burnelli, Roberta; Panareo, Stefano; Scalorbi, Federica; Rambaldi, Ilaria; Piccardo, Arnoldo; Garaventa, Alberto; Familiari, Demetrio; Fornito, Maria Concetta; Lopci, Egesta; Mascarin, Maurizio; Altini, Corinna; Ferrari, Cristina; Perillo, Teresa; Santoro, Nicola; Borsatti, Eugenio; Rubini, Giuseppe

2018-06-01

The present study investigated the utility of fluorine-18 ( 18 F) fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL). A total of 224 pediatric patients with HL underwent 18 F-FDG PET/CT at staging. BMB or follow-up imaging was used as the standard of reference for the evaluation of BMI. 18 F-FDG PET/CT was negative for BMI in 193 cases. Of the 193 patients, the findings for 16 were originally reported as doubtful and later interpreted as negative for BMI, with negative findings on follow-up imaging and BMB. At BMB, 1 of the 16 patients (6.25%) had BMI. Of the 193 patients, 192 (99.48%) had negative BMB findings. Thus, the 18 F-FDG PET/CT findings were truly negative for 192 patients and falsely negative for 1 patient for BMI. 18 F-FDG PET/CT showed high diagnostic performance in the evaluation of BMI in pediatric HL. Thus, BMB should be ideally reserved for patients presenting with doubtful 18 F-FDG PET/CT findings for BMI. Copyright © 2018 Elsevier Inc. All rights reserved.

A survey of recommendations given to patients going home after bone marrow transplant.

PubMed Central

Brandt, L; Broadbent, V

1994-01-01

A postal questionnaire was sent to 11 UK Children's Cancer Study Group bone marrow transplant centres asking them for details of their instructions to patients on discharge after either allogeneic or auto transplant; nine centres responded. There was no recommendation on which they all agreed. Though all centres gave prophylactic septrin, the times of starting and stopping treatment varied considerably. Three centres recommended lifelong penicillin after total body irradiation, one treated for two years and five gave no such prophylaxis. Four of nine centres gave routine acyclovir for herpes simplex prophylaxis. Most centres suggested prophylaxis against varicella after contact exposure for one year. However, three gave zoster immune globulin alone, one gave this together with acyclovir, and five gave acyclovir alone. No two centres recommended the same dose of acyclovir. Vaccinations were allowed from 6-18 months after transplant. One centre required documentation of recovery of immune function first. Four centres recommended a child stay off school for six months; others had 'common sense' approaches. Only one centre did not allow family holidays for the first six months but many imposed restrictions on these holidays. Dietary restrictions varied greatly between centres. It is concluded that there is a need for unified and scientifically justified guidelines after transplant for paediatric bone marrow transplant patients. PMID:7726614

Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla.

PubMed

Liney, Gary P; Bernard, Clare P; Manton, David J; Turnbull, Lindsay W; Langton, Chris M

2007-09-01

To evaluate the efficacy of MR Spectroscopy (MRS) at 3.0 Tesla for the assessment of normal bone marrow composition and assess the variation in terms of age, gender, and skeletal site. A total of 16 normal subjects (aged between eight and 57 years) were investigated on a 3.0 Tesla GE Signa system. To investigate axial and peripheral skeleton differences, non-water-suppressed spectra were acquired from single voxels in the calcaneus and lumbar spine. In addition, spectra were acquired at multiple vertebral bodies to assess variation within the lumbar spine. Data was also correlated with bone mineral density (BMD) measured in six subjects using dual-energy X-ray absorptiometry (DXA). Fat content was an order of magnitude greater in the heel compared to the spine. An age-related increase was demonstrated in the spine with values greater in men compared to female subjects. Significant trends in vertebral bodies within the same subjects were also shown, with fat content increasing L5 > L1. Population coefficient of variation (CV) was greater for fat fraction (FF) compared to BMD. Significant normal variations of marrow composition have been demonstrated, which provide important data for the future interpretation of patient investigations. (c) 2007 Wiley-Liss, Inc.

[Responses of Cynodon dactylon population in hydro-fluctuation belt of Three Gorges Reservoir area to flooding-drying habitat change].

PubMed

Hong, Ming; Guo, Quan-Shu; Nie, Bi-Hong; Kang, Yi; Pei, Shun-Xiang; Jin, Jiang-Qun; Wang, Xiang-Fu

2011-11-01

This paper studied the population density, morphological characteristics, and biomass and its allocation of Cynodon dactylon at different altitudinal sections of the hydro-fluctuation belt in Three Gorges Reservoir area, based on located observations. At the three altitudinal sections, the population density of C. dactylon was in the order of shallow water section (165-170 m elevation) > non-flooded section (above 172 m elevation) > deep water section (145-150 m elevation), the root diameter and root length were in the order of deep water section > shallow water section > non-flooded section, the total biomass, root biomass, stem biomass, leaf biomass, and stem biomass allocation ratio were in the order of the shallow water section > non-flooded section > deep water section, and the root biomass allocation ratio, leaf biomass allocation ratio, and underground biomass/aboveground biomass were in the order of deep water section > shallow water section > non-flooded section. The unique adaption strategies of C. dactylon to the flooding-drying habitat change in the shallow water section were the accelerated elongation growth and the increased stem biomass allocation, those in the deep water section were the increased node number of primary and secondary branches, increased number of the branches, and increased leaf biomass allocation, whereas the common strategies in the shallow and deep water sections were the accelerated root growth and the increased tillering and underground biomass allocation for preparing nutrition and energy for the rapid growth in terrestrial environment.

Drinking water quality assessment in Southern Sindh (Pakistan).

PubMed

Memon, Mehrunisa; Soomro, Mohammed Saleh; Akhtar, Mohammad Saleem; Memon, Kazi Suleman

2011-06-01

The southern Sindh province of Pakistan adjoins the Arabian Sea coast where drinking water quality is deteriorating due to dumping of industrial and urban waste and use of agrochemicals and yet has limited fresh water resources. The study assessed the drinking water quality of canal, shallow pumps, dug wells, and water supply schemes from the administrative districts of Thatta, Badin, and Thar by measuring physical, chemical, and biological (total coliform) quality parameters. All four water bodies (dug wells, shallow pumps canal water, and water supply schemes) exceeded WHO MPL for turbidity (24%, 28%, 96%, 69%), coliform (96%, 77%, 92%, 81%), and electrical conductivity (100%, 99%, 44%, 63%), respectively. However, the turbidity was lower in underground water, i.e., 24% and 28% in dug wells and shallow pumps as compared to open water, i.e., 96% and 69% in canal and water supply schemes, respectively. In dug wells and shallow pumps, limits for TDS, alkalinity, hardness, and sodium exceeded, respectively, by 63% and 33%; 59% and 70%, 40% and 27%, and 78% and 26%. Sodium was major problem in dug wells and shallow pumps of district Thar and considerable percent in shallow pumps of Badin. Iron was major problem in all water bodies of district Badin ranging from 50% to 69% and to some extent in open waters of Thatta. Other parameters as pH, copper, manganese, zinc, and phosphorus were within standard permissible limits of World Health Organization. Some common diseases found in the study area were gastroenteritis, diarrhea and vomiting, kidney, and skin problems.

Discriminating a deep gallium antisite defect from shallow acceptors in GaAs using supercell calculations

DOE PAGES

Schultz, Peter A.

2016-03-01

For the purposes of making reliable first-principles predictions of defect energies in semiconductors, it is crucial to distinguish between effective-mass-like defects, which cannot be treated accurately with existing supercell methods, and deep defects, for which density functional theory calculations can yield reliable predictions of defect energy levels. The gallium antisite defect GaAs is often associated with the 78/203 meV shallow double acceptor in Ga-rich gallium arsenide. Within a conceptual framework of level patterns, analyses of structure and spin stabilization can be used within a supercell approach to distinguish localized deep defect states from shallow acceptors such as B As. Thismore » systematic approach determines that the gallium antisite supercell results has signatures inconsistent with an effective mass state and cannot be the 78/203 shallow double acceptor. Lastly, the properties of the Ga antisite in GaAs are described, total energy calculations that explicitly map onto asymptotic discrete localized bulk states predict that the Ga antisite is a deep double acceptor and has at least one deep donor state.« less

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies.

PubMed

Plaizier, M A; Roos, J C; Teule, G J; van Dieren, E B; den Hollander, W; Haisma, H J; DeJager, R L; van Lingen, A

1994-03-01

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium-111-OV-TL-3 F(ab')2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111In-OV-TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16.88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

PubMed Central

Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

2012-01-01

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

Eutrophication effects on greenhouse gas fluxes from shallow-lake mesocosms override those of climate warming.

PubMed

Davidson, Thomas A; Audet, Joachim; Svenning, Jens-Christian; Lauridsen, Torben L; Søndergaard, Martin; Landkildehus, Frank; Larsen, Søren E; Jeppesen, Erik

2015-12-01

Fresh waters make a disproportionately large contribution to greenhouse gas (GHG) emissions, with shallow lakes being particular hot spots. Given their global prevalence, how GHG fluxes from shallow lakes are altered by climate change may have profound implications for the global carbon cycle. Empirical evidence for the temperature dependence of the processes controlling GHG production in natural systems is largely based on the correlation between seasonal temperature variation and seasonal change in GHG fluxes. However, ecosystem-level GHG fluxes could be influenced by factors, which while varying seasonally with temperature are actually either indirectly related (e.g. primary producer biomass) or largely unrelated to temperature, for instance nutrient loading. Here, we present results from the longest running shallow-lake mesocosm experiment which demonstrate that nutrient concentrations override temperature as a control of both the total and individual GHG flux. Furthermore, testing for temperature treatment effects at low and high nutrient levels separately showed only one, rather weak, positive effect of temperature (CH4 flux at high nutrients). In contrast, at low nutrients, the CO2 efflux was lower in the elevated temperature treatments, with no significant effect on CH4 or N2 O fluxes. Further analysis identified possible indirect effects of temperature treatment. For example, at low nutrient levels, increased macrophyte abundance was associated with significantly reduced fluxes of both CH4 and CO2 for both total annual flux and monthly observation data. As macrophyte abundance was positively related to temperature treatment, this suggests the possibility of indirect temperature effects, via macrophyte abundance, on CH4 and CO2 flux. These findings indicate that fluxes of GHGs from shallow lakes may be controlled more by factors indirectly related to temperature, in this case nutrient concentration and the abundance of primary producers. Thus, at ecosystem scale, response to climate change may not follow predictions based on the temperature dependence of metabolic processes. © 2015 John Wiley & Sons Ltd.

Spatial characteristics of cadmium in topsoils in a typical e-waste recycling area in southeast China and its potential threat to shallow groundwater.

PubMed

Wu, Chunfa; Luo, Yongming; Deng, Shaopo; Teng, Ying; Song, Jing

2014-02-15

Informal electrical and electronic waste (e-waste) recycling often creates secondary sources of cadmium (Cd) pollution. To characterize the total Cd concentration (Cdtotal) in topsoil and evaluate the threat of Cd in topsoils to shallow groundwater, 187 topsoil samples and 12 shallow groundwater samples were collected in a typical e-waste recycling area in southeast China. Soil organic matter content, soil pH and Cdtotal in topsoil, pH and dissolved Cd concentration in shallow groundwater were measured. Cdtotal in the topsoils showed an inverse distribution trend with soil pH in that high Cd concentrations (and low pH values) were found in the surrounding area of the metal recycling industrial park where there were many family-operated e-waste recycling facilities before the industrial park was established and with low concentrations (and high pH values) in other areas, and they had similar spatial correlation structures. Cd accumulation and acidification were synchronous in topsoils, and soil pH was significantly correlated with Cdtotal in topsoils with low to moderate negative correlation coefficient (r=-0.24), indicating that both of them maybe correlated with informal recycling. The shallow groundwater in the surrounding area of the metal recycling industrial park was seriously contaminated by Cd, and topsoil Cd accumulation and acidification in the surrounding area of e-waste recycling sites significantly increase the risk of shallow groundwater contaminated by Cd. Action is urgently required to control Cd accumulation and acidification by improving the recycling operations of e-wastes in order to reduce the risk of Cd leaching from topsoils and shallow groundwater contamination. Copyright © 2013. Published by Elsevier B.V.

Higher species richness of octocorals in the upper mesophotic zone in Eilat (Gulf of Aqaba) compared to shallower reef zones

NASA Astrophysics Data System (ADS)

Shoham, Erez; Benayahu, Yehuda

2017-03-01

Mesophotic coral-reef ecosystems (MCEs), which comprise the light-dependent communities of corals and other organisms found at depths between 30 and 150 m, have received very little study to date. However, current technological advances, such as remotely operated vehicles and closed-circuit rebreather diving, now enable their thorough investigation. Following the reef-building stony corals, octocorals are the second most common benthic component on many shallow reefs and a major component on deep reefs, the Red Sea included. This study is the first to examine octocoral community features on upper MCEs based on species-level identification and to compare them with the shallower reef zones. The study was carried out at Eilat (Gulf of Aqaba, northern Red Sea), comparing octocoral communities at two mesophotic reefs (30-45 m) and two shallow reef zones (reef flat and upper fore-reef) by belt transects. A total of 30 octocoral species were identified, with higher species richness on the upper MCEs compared to the shallower reefs. Although the MCEs were found to host a higher number of species than the shallower reefs, both featured a similar diversity. Each reef zone revealed a unique octocoral species composition and distinct community structure, with only 16% of the species shared by both the MCEs and the shallower reefs. This study has revealed an almost exclusive dominance of zooxanthellate species at the studied upper MCE reefs, thus indicating an adequate light regime for photosynthesis there. The findings should encourage similar studies on other reefs, aimed at understanding the spatiotemporal features and ecological role of octocorals in reef ecosystems down to the deepest limit of the MCEs.

Dealing With Shallow-Water Flow in the Deepwater Gulf of Mexico

NASA Astrophysics Data System (ADS)

Ostermeier, R.

2006-05-01

Some of the Shell experience in dealing with the shallow-water flow problem in the Deepwater Gulf of Mexico (GOM) will be presented. The nature of the problem, including areal extent and over-pressuring mechanisms, will be discussed. Methods for sand prediction and shallow sediment and flow characterization will be reviewed. These include seismic techniques, the use of geo-technical wells, regional trends, and various MWD methods. Some examples of flow incidents with pertinent drilling issues, including well failures and abandonment, will be described. To address the shallow-water flow problem, Shell created a multi-disciplinary team of specialists in geology, geophysics, petrophysics, drilling, and civil engineering. The team developed several methodologies to deal with various aspects of the problem. These include regional trends and data bases, shallow seismic interpretation and sand prediction, well site and casing point selection, geo-technical well design and data interpretation, logging program design and interpretation, cementing design and fluids formulation, methods for remediation and mitigation of lost circulation, and so on. Shell's extensive Deepwater GOM drilling experience has lead to new understanding of the problem. Examples include delineation of trends in shallow water flow occurrence and severity, trends and departures in PP/FG, rock properties pertaining to seismic identification of sands, and so on. New knowledge has also been acquired through the use of geo-technical wells. One example is the observed rapid onset and growth of over-pressures below the mudline. Total trouble costs due to shallow water flow for all GOM operators almost certainly runs into the several hundred million dollars. Though the problem remains a concern, advances in our knowledge and understanding make it a problem that is manageable and not the "show stopper" once feared.

Cultivation-Independent and Cultivation-Dependent Analysis of Microbes in the Shallow-Sea Hydrothermal System Off Kueishantao Island, Taiwan: Unmasking Heterotrophic Bacterial Diversity and Functional Capacity.

PubMed

Tang, Kai; Zhang, Yao; Lin, Dan; Han, Yu; Chen, Chen-Tung A; Wang, Deli; Lin, Yu-Shih; Sun, Jia; Zheng, Qiang; Jiao, Nianzhi

2018-01-01

Shallow-sea hydrothermal systems experience continuous fluctuations of physicochemical conditions due to seawater influx which generates variable habitats, affecting the phylogenetic composition and metabolic potential of microbial communities. Until recently, studies of submarine hydrothermal communities have focused primarily on chemolithoautotrophic organisms, however, there have been limited studies on heterotrophic bacteria. Here, fluorescence in situ hybridization, high throughput 16S rRNA gene amplicon sequencing, and functional metagenomes were used to assess microbial communities from the shallow-sea hydrothermal system off Kueishantao Island, Taiwan. The results showed that the shallow-sea hydrothermal system harbored not only autotrophic bacteria but abundant heterotrophic bacteria. The potential for marker genes sulfur oxidation and carbon fixation were detected in the metagenome datasets, suggesting a role for sulfur and carbon cycling in the shallow-sea hydrothermal system. Furthermore, the presence of diverse genes that encode transporters, glycoside hydrolases, and peptidase indicates the genetic potential for heterotrophic utilization of organic substrates. A total of 408 cultivable heterotrophic bacteria were isolated, in which the taxonomic families typically associated with oligotrophy, copiotrophy, and phototrophy were frequently found. The cultivation-independent and -dependent analyses performed herein show that Alphaproteobacteria and Gammaproteobacteria represent the dominant heterotrophs in the investigated shallow-sea hydrothermal system. Genomic and physiological characterization of a novel strain P5 obtained in this study, belonging to the genus Rhodovulum within Alphaproteobacteria, provides an example of heterotrophic bacteria with major functional capacity presented in the metagenome datasets. Collectively, in addition to autotrophic bacteria, the shallow-sea hydrothermal system also harbors many heterotrophic bacteria with versatile genetic potential to adapt to the unique environmental conditions.

Cultivation-Independent and Cultivation-Dependent Analysis of Microbes in the Shallow-Sea Hydrothermal System Off Kueishantao Island, Taiwan: Unmasking Heterotrophic Bacterial Diversity and Functional Capacity

PubMed Central

Tang, Kai; Zhang, Yao; Lin, Dan; Han, Yu; Chen, Chen-Tung A.; Wang, Deli; Lin, Yu-Shih; Sun, Jia; Zheng, Qiang; Jiao, Nianzhi

2018-01-01

Shallow-sea hydrothermal systems experience continuous fluctuations of physicochemical conditions due to seawater influx which generates variable habitats, affecting the phylogenetic composition and metabolic potential of microbial communities. Until recently, studies of submarine hydrothermal communities have focused primarily on chemolithoautotrophic organisms, however, there have been limited studies on heterotrophic bacteria. Here, fluorescence in situ hybridization, high throughput 16S rRNA gene amplicon sequencing, and functional metagenomes were used to assess microbial communities from the shallow-sea hydrothermal system off Kueishantao Island, Taiwan. The results showed that the shallow-sea hydrothermal system harbored not only autotrophic bacteria but abundant heterotrophic bacteria. The potential for marker genes sulfur oxidation and carbon fixation were detected in the metagenome datasets, suggesting a role for sulfur and carbon cycling in the shallow-sea hydrothermal system. Furthermore, the presence of diverse genes that encode transporters, glycoside hydrolases, and peptidase indicates the genetic potential for heterotrophic utilization of organic substrates. A total of 408 cultivable heterotrophic bacteria were isolated, in which the taxonomic families typically associated with oligotrophy, copiotrophy, and phototrophy were frequently found. The cultivation-independent and -dependent analyses performed herein show that Alphaproteobacteria and Gammaproteobacteria represent the dominant heterotrophs in the investigated shallow-sea hydrothermal system. Genomic and physiological characterization of a novel strain P5 obtained in this study, belonging to the genus Rhodovulum within Alphaproteobacteria, provides an example of heterotrophic bacteria with major functional capacity presented in the metagenome datasets. Collectively, in addition to autotrophic bacteria, the shallow-sea hydrothermal system also harbors many heterotrophic bacteria with versatile genetic potential to adapt to the unique environmental conditions. PMID:29527196

Watershed vs. within-lake drivers of nitrogen: phosphorus dynamics in shallow lakes.

PubMed

Ginger, Luke J; Zimmer, Kyle D; Herwig, Brian R; Hanson, Mark A; Hobbs, William O; Small, Gaston E; Cotner, James B

2017-10-01

Research on lake eutrophication often identifies variables affecting amounts of phosphorus (P) and nitrogen (N) in lakes, but understanding factors influencing N:P ratios is important given its influence on species composition and toxin production by cyanobacteria. We sampled 80 shallow lakes in Minnesota (USA) for three years to assess effects of watershed size, proportion of watershed as both row crop and natural area, fish biomass, and lake alternative state (turbid vs. clear) on total N : total P (TN : TP), ammonium, total dissolved phosphorus (TDP), and seston stoichiometry. We also examined N:P stoichiometry in 20 additional lakes that shifted states during the study. Last, we assessed the importance of denitrification by measuring denitrification rates in sediment cores from a subset of 34 lakes, and by measuring seston δ 15 N in four additional experimental lakes before and after they were experimentally manipulated from turbid to clear states. Results showed alternative state had the largest influence on overall N:P stoichiometry in these systems, as it had the strongest relationship with TN : TP, seston C:N:P, ammonium, and TDP. Turbid lakes had higher N at given levels of P than clear lakes, with TN and ammonium 2-fold and 1.4-fold higher in turbid lakes, respectively. In lakes that shifted states, TN was 3-fold higher in turbid lakes, while TP was only 2-fold higher, supporting the notion N is more responsive to state shifts than is P. Seston δ 15 N increased after lakes shifted to clear states, suggesting higher denitrification rates may be important for reducing N levels in clear states, and potential denitrification rates in sediment cores were among the highest recorded in the literature. Overall, our results indicate lake state was a primary driver of N:P dynamics in shallow lakes, and lakes in clear states had much lower N at a given level of P relative to turbid lakes, likely due to higher denitrification rates. Shallow lakes are often managed for the clear-water state due to increased value as wildlife habitat. However, our results indicate lake state also influences N biogeochemistry, such that managing shallow lakes for the clear-water state may also mitigate excess N levels at a landscape scale. © 2017 by the Ecological Society of America.

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Meeting report of the 2016 bone marrow adiposity meeting

PubMed Central

van der Eerden, Bram; van Wijnen, André

2017-01-01

Abstract There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies. PMID:28410005

Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system.

PubMed

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

2018-03-16

Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R -/- (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat's remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.

Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia.

PubMed

Mamrak, Nicholas E; Shimamura, Akiko; Howlett, Niall G

2017-05-01

Fanconi anemia (FA) is a rare autosomal and X-linked genetic disease characterized by congenital abnormalities, progressive bone marrow failure (BMF), and increased cancer risk during early adulthood. The median lifespan for FA patients is approximately 33years. The proteins encoded by the FA genes function together in the FA-BRCA pathway to repair DNA damage and to maintain genome stability. Within the past two years, five new FA genes have been identified-RAD51/FANCR, BRCA1/FANCS, UBE2T/FANCT, XRCC2/FANCU, and REV7/FANCV-bringing the total number of disease-causing genes to 21. This review summarizes the discovery of these new FA genes and describes how these proteins integrate into the FA-BRCA pathway to maintain genome stability and critically prevent early-onset BMF and cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hereditary dyserythropoiesis with abnormal membrane folate transport.

PubMed

Howe, R B; Branda, R F; Douglas, S D; Brunning, R D

1979-11-01

Dyserythropoiesis, which morphologically and serologically resembles congenital dyserythropoietic anemia type III but is not accompanied by anemia, is described in a young man. In addition to striking gigantism and multinuclearity of erythroid precursors, electron microscopy revealed widening of nuclear pores, nuclear clefts, and cytoplasmic inclusions. Membrane transport of 5-methyltetrahydrofolate by the patient's red cells was markedly reduced; total uptake, uptake velocity, and maximal velocity of uptake were all significantly less than in controls. In contrast, red cell uptake of pteroylglutamic acid was normal. Bone marrow cells in culture also showed decreased 5-methyltetrahydrofolate uptake, as well as very low thymidine incorporation. Because folate uptake by mitogen-stimulated lymphocytes was normal, the defect apparently does not involve all cell lines. These results suggest that a specific membrane defect, affecting the carrier system for reduced folate compounds, is present in this patient's erythrocytes, and perhaps, their bone marrow precursors.

Trends in nitrogen concentration and nitrogen loads entering the South Shore Estuary Reserve from streams and ground-water discharge in Nassau and Suffolk counties, Long Island, New York, 1952–97

USGS Publications Warehouse

Monti, Jack; Scorca, Michael P.

2003-01-01

The 13 major south-shore streams in Nassau and Suffolk Counties, Long Island, New York with adequate long-term (1971-97) water-quality records, and 192 south-shore wells with sufficient water-quality data, were selected for analysis of geographic, seasonal, and long-term trends in nitrogen concentration. Annual total nitrogen loads transported to the South Shore Estuary Reserve (SSER) from 11 of these streams were calculated using long-term discharge records. Nitrogen loads from shallow and deep ground water also were calculated using simulated ground-water discharge of 1968-83 hydrologic conditions.Long-term declines in stream discharge occurred in East Meadow Brook, Bellmore Creek and Massapequa Creek in response to extensive sewering in Nassau County. The smallest longterm annual discharge to the SSER was from the westernmost stream, Pines Brook, which is in an area in which the water table has been lowered by sewers since 1952. The three largest average annual discharges to the SSER were from the Connetquot River, Carlls River, and Carmans River in Suffolk County; the discharges from each of these streams were at least twice those of the other streams considered in this study.Total nitrogen concentrations in streams show a geographic trend with a general eastward increase in median total nitrogen concentration in Nassau County and a decreasing trend from Massapequa Creek eastward into Suffolk County. Total nitrogen concentrations in streams generally are lowest during summer and highest in winter as a result of seasonal fluctuations in chemical reactions and biological activity. The greatest seasonal difference in median total nitrogen concentration was at Carlls River with values of 3.4 and 4.2 mg/L (milligrams per liter) as N during summer (April through September) and winter (October through March), respectively. Streams affected by the completion of sewer districts show long-term (1971-97) trends of decreasing total nitrogen concentration and streams showing an increase in total nitrogen concentration are in unsewered areas with increased urbanization.Discharges from shallow ground water (upper glacial aquifer) and deep ground water (upper part of Magothy aquifer) were simulated from a ground-water-flow model calibrated to steadystate (1968-83) conditions. Simulated discharges from shallow-ground-water system in Nassau County were 10,700 Mgal/yr (million gallons per year) or 40,500,000 m3/yr (cubic meters per year), and those from Suffolk County were 52,300 Mgal/yr or 198,000,000 m3/yr. Discharges from deep-ground-water system in Nassau County were 4,900 Mgal/yr or 18,500,000 m3/yr, and those in Suffolk County were 12,700 Mgal/yr or 48,200,000 m3/yr.Ground-water concentrations of nitrogen decrease with depth and from west to east. The shallow ground water median nitrogen concentration for each county was determined using 1,155 samples collected at 167 shallow wells (125 feet deep or less) within 1 mile of the shore. The deep ground water median nitrate concentration (nitrate represented almost all of the total nitrogen) for each county was determined using 112 samples collected at 25 deep wells (greater than 125 feet deep) within 1 mile of the shore. The median nitrogen concentration for the shallow and median nitrate concentration for the deep ground water in Nassau County were 3.85 and 0.15 mg/L as N, during 1952–97; the corresponding concentrations for Suffolk County were 1.74 and <0.10 (less than 0.10) mg/L as N, during 1952–97.Nitrogen loads discharged from streams to the SSER for each year during 1972–97 were calculated as the annual total nitrogen concentration multiplied by the annual discharge. These values were calculated only for the seven streams for which sufficient data were available. The largest long-term (1972–97) average annual nitrogen load from Carlls River was 104 ton/yr or 94,300 kg/yr—about twice that of Connetquot River (54 ton/yr or 48,900 kg/yr) and over three times that of Carmans River (33 ton/yr or 29,900 kg/yr). The smallest annual mean nitrogen load was from Pines Brook, which has the lowest annual mean discharge of all streams analyzed.The nitrogen load carried to the SSER by ground-water discharge in shallow-ground-water system in Nassau and Suffolk Counties was calculated as the simulated discharge for each county multiplied by the respective median nitrogen concentration, and loads from deep-ground-water system were calculated as the simulated discharge for each county multiplied by the respective median nitrate concentration. All discharges were obtained from the U.S. Geological Survey's Long Island ground-water-flow model. The resultant nitrogen loads discharged to the SSER from shallow ground water were 172 ton/yr (156,000 kg/yr) from Nassau County and 380 ton/yr (345,000 kg/yr) from Suffolk County; equaling 552 ton/yr entering the SSER. Those from deep ground water were 3 ton/yr (2,700 kg/yr) from Nassau County and <0.5 ton/yr (480 kg/yr) from Suffolk County; equaling about 3.5 ton/yr entering the SSER.The sum of both stream loads and groundwater loads results in the total load to the SSER. The largest calculated total nitrogen load entering the SSER from both streams and ground water occurred in 1979 with a total load of 1,260 ton/yr (1,140,000 kg/yr). The smallest calculated nitrogen load entering the SSER occurred in 1995 with a total load of 725 ton/yr (658,000 kg/yr).

Evaluation of bone marrow aspirates in patients with acute myeloid leukemia at day 14 of induction therapy.

PubMed

Souto Filho, João Tadeu D; Loureiro, Monique M; Pulcheri, Wolmar; Morais, José Carlos; Nucci, Marcio; Portugal, Rodrigo D

2015-07-25

Early assessment of response to chemotherapy in acute myeloid leukemia may be performed by examining bone marrow aspirate (BMA) or biopsy (BMB); a hypocellular bone marrow sample indicates adequate anti-leukemic activity. We sought to evaluate the quantitative and qualitative assessment of BMA performed on day 14 (D14) of chemotherapy, to verify the inter-observer agreement, to compare the results of BMA and BMB, and to evaluate the impact of D14 blast clearance on the overall survival (OS). A total of 107 patients who received standard induction chemotherapy and had bone marrow samples were included. BMA evaluation was performed by two observers using two methods: quantitative assessment and a qualitative (Likert) scale. ROC curves were obtained correlating the BMA quantification of blasts and the qualitative scale, by both observers, with BMB result as gold-standard. There was a significant agreement between the two observers in both the qualitative and quantitative assessments (Kw = 0.737, p < 0.001, and rs = 0.798, p < 0.001; ICC = 0.836, p < 0.001, respectively). The areas under the curve (AUC) were 0.924 and 0.946 for observer 1 and 0.867 and 0.870 for observer 2 for assessments of the percentage of blasts and qualitative scale, respectively. The best cutoff for blast percentage in BMA was 6% and 7% for observers 1 and 2, respectively. A similar analysis for the qualitative scale showed the best cutoff as "probably infiltrated". Patients who attained higher grades of cytoreduction on D14 had better OS. Evaluation of D14 BMA using both methods had a significant agreement with BMB and between observers, identifying a population of patients with poor outcome.

Prevalence and aetiology of anaemia in lymphoid malignancies.

PubMed

Ghosh, J; Singh, R K Bikramjit; Saxena, R; Gupta, R; Vivekanandan, S; Sreenivas, V; Raina, V; Sharma, A; Kumar, L

2013-01-01

We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies. Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the prevalence and a subgroup of 46 patients was analysed for the cause of anaemia. Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients. Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out. Copyright 2013, NMJI.

Induction of IgA B cell differentiation of bone marrow-derived B cells by Peyer's patch autoreactive helper T cells.

PubMed

Kihira, T; Kawanishi, H

1995-08-01

The objective of this study was to demonstrate in vitro that bone marrow-derived pro/pre-B cells bearing mu mRNA can switch their Ig heavy-chain isotype to that of alpha mRNA-expressing B cells after contact with Peyer's patches-derived activated autoreactive CD4+ T cells. Bone marrow-derived pro/pre-B cells and activated autoreactive Peyer's patch, mesenteric lymph node, or spleen CD4+ T cells were co-cultured in the presence of recombinant (r) IL-2, rIL-7, and Con A for 3 days. The mixed cultured cells were isolated for preparation of total RNA. Dot/slot hybridization, using murine C mu (pu3741) and C alpha (P alpha J558) Ig heavy-chain cDNA probes, detected C mu and C alpha Ig heavy-chain mRNA transcripts. The magnitude of each mRNA expression was measured demsitometrically. In addition, the secreted class-specific Ig contents from the co-cultured supernatants were measured. The results indicate that activated autoreactive Peyer's patch and mesenteric lymph node CD4+ T cells provide a specific Ig heavy-chain switch from mu to alpha (Peyer's patch CD4+ T cells > mesenteric lymph node CD4+ T cells) in bone marrow-derived pro/pre-B cells and also assist to develop IgA-secreting plasma cells. The alpha heavy-chain switch and IgA production do not occur in the presence of activated autoreactive spleen CD4+ T cells. These results support the view that autoreactive gut Peyer's patch CD4+ T cells, at least, regulate IgA B cell heavy-chain switching and terminal differentiation during gut mucosal B cell development.

High levels of circulating triiodothyronine induce plasma cell differentiation.

PubMed

Bloise, Flavia Fonseca; Oliveira, Felipe Leite de; Nobrega, Alberto Félix; Vasconcellos, Rita; Cordeiro, Aline; Paiva, Luciana Souza de; Taub, Dennis D; Borojevic, Radovan; Pazos-Moura, Carmen Cabanelas; Mello-Coelho, Valéria de

2014-03-01

The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3'-triiodothyronine (T3) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T3 for 14 days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19(+)B-cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220(+) cells correlating with an increased percentage of CD138(+) plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulin-secreting B-cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T3. In conclusion, we provide evidence that high-circulating levels of T3 stimulate plasma cytogenesis favoring an increase in plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.

Osteoblastic phenotype of rat marrow stromal cells cultured in the presence of dexamethasone, beta-glycerolphosphate, and L-ascorbic acid

NASA Technical Reports Server (NTRS)

Peter, S. J.; Liang, C. R.; Kim, D. J.; Widmer, M. S.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

1998-01-01

We investigated the effects of the time course of addition of osteogenic supplements dexamethasone, beta-glycerolphosphate, and L-ascorbic acid to rat marrow stromal cells, and the exposure time on the proliferation and differentiation of the cells. It was the goal of these experiments to determine the time point for supplement addition to optimize marrow stromal cell proliferation and osteoblastic differentiation. To determine this, two studies were performed; one study was based on the age of the cells from harvest, and the other study was based on the duration of exposure to supplemented medium. Cells were seen to proliferate rapidly at early time points in the presence and absence of osteogenic supplements as determined by 3H-thymidine incorporation into the DNA of replicating cells. These results were supported by cell counts ascertained through total DNA analysis. Alkaline phosphatase (ALP) activity and osteocalcin production at 21 days were highest for both experimental designs when the cells were exposed to supplemented medium immediately upon harvest. The ALP levels at 21 days were six times greater for cells maintained in supplements throughout than for control cells cultured in the absence of supplements for both studies, reaching an absolute value of 75 x 10(-7) micromole/min/cell. Osteocalcin production reached 20 x 10(-6) ng/cell at 21 days in both studies for cells maintained in supplemented medium throughout the study, whereas the control cells produced an insignificant amount of osteocalcin. These results suggest that the addition of osteogenic supplements to marrow-derived cells early in the culture period did not inhibit proliferation and greatly enhanced the osteoblastic phenotype of cells in a rat model.

Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation?

PubMed

Milburn, H J; Prentice, H G; du Bois, R M

1992-06-01

Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain. Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis. Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph. Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs.

Hydrochemical evaluation and identification of geochemical processes in the shallow and deep wells in the Ramganga Sub-Basin, India.

PubMed

Rajmohan, Natarajan; Patel, Neelam; Singh, Gaurav; Amarasinghe, Upali A

2017-09-01

Groundwater samples were collected from 44 wells in the Ramganga Sub-Basin (RSB), India, and analysed for major ions, nutrients and trace metals. The primary goal of this study is to evaluate the hydrochemistry and to identify the geochemical processes that govern the water chemistry in the shallow and deep tube wells in the study area using geochemical methods. The knowledge of changes in hydrochemistry of the aquifers is important for both groundwater recharge and use in the region. This study found that there are substantial differences of water chemistry between shallow and deep wells. In the shallow wells, the average concentrations of total dissolved solid (TDS), Na, K, Ca, Mg, HCO 3 , Cl, SO 4 , NO 3 , PO 4 , F, Cu, Mn, Fe and Cr are twofold higher than the deep wells. The concentrations of dissolved silica in the groundwater do not vary with the depth, which implies that the variation in the water chemistry is not due to mineral dissolution alone. Major ion ratios and saturation indices suggest that the water chemistry is predominantly controlled by dissolution of carbonate minerals, silicate weathering and ion exchange reactions. Thermodynamic evaluation (ion activity ratios and stability filed diagrams) indicates that the kaolinite and gibbsite controlled the water chemistry in the both shallow and deep wells. In addition, the groundwater chemistry in the shallow wells is affected by the vertical infiltration of contaminated water from surface contamination sources and nitrification process. In the deep wells, absence of NO 3 and low concentrations of Cl, SO 4 , PO 4 and F imply the role of regional flow and denitrification in the groundwater. Results concluded that proper management plan is necessary to protect the shallow aquifer in the RSB since shallow aquifer pumping is less expensive than the deeper one.

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.

Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

PubMed Central

Eichler, Hermann; Orth, Patrick

2017-01-01

Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed. PMID:28607559

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

PubMed Central

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

Combined Administration of Recombinant Human Megakaryocyte Growth and Development Factor and Granulocyte Colony-Stimulating Factor Enhances Multilineage Hematopoietic Reconstitution in Nonhuman Primates after Radiation-Induced Marrow Aplasia

DTIC Science & Technology

1996-05-01

dose would yield an equivalent or better biological activity. Neupogen ® ( Filgrastim ), r-metHuG-CSF, was produced in E. coli as a...recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoi- etic recovery after otherwise lethal total body

Total energy and potential enstrophy conserving schemes for the shallow water equations using Hamiltonian methods - Part 1: Derivation and properties

NASA Astrophysics Data System (ADS)

Eldred, Christopher; Randall, David

2017-02-01

The shallow water equations provide a useful analogue of the fully compressible Euler equations since they have similar characteristics: conservation laws, inertia-gravity and Rossby waves, and a (quasi-) balanced state. In order to obtain realistic simulation results, it is desirable that numerical models have discrete analogues of these properties. Two prototypical examples of such schemes are the 1981 Arakawa and Lamb (AL81) C-grid total energy and potential enstrophy conserving scheme, and the 2007 Salmon (S07) Z-grid total energy and potential enstrophy conserving scheme. Unfortunately, the AL81 scheme is restricted to logically square, orthogonal grids, and the S07 scheme is restricted to uniform square grids. The current work extends the AL81 scheme to arbitrary non-orthogonal polygonal grids and the S07 scheme to arbitrary orthogonal spherical polygonal grids in a manner that allows for both total energy and potential enstrophy conservation, by combining Hamiltonian methods (work done by Salmon, Gassmann, Dubos, and others) and discrete exterior calculus (Thuburn, Cotter, Dubos, Ringler, Skamarock, Klemp, and others). Detailed results of the schemes applied to standard test cases are deferred to part 2 of this series of papers.

Coupled three-layer model for turbulent flow over large-scale roughness: On the hydrodynamics of boulder-bed streams

NASA Astrophysics Data System (ADS)

Pan, Wen-hao; Liu, Shi-he; Huang, Li

2018-02-01

This study developed a three-layer velocity model for turbulent flow over large-scale roughness. Through theoretical analysis, this model coupled both surface and subsurface flow. Flume experiments with flat cobble bed were conducted to examine the theoretical model. Results show that both the turbulent flow field and the total flow characteristics are quite different from that in the low gradient flow over microscale roughness. The velocity profile in a shallow stream converges to the logarithmic law away from the bed, while inflecting over the roughness layer to the non-zero subsurface flow. The velocity fluctuations close to a cobble bed are different from that of a sand bed, and it indicates no sufficiently large peak velocity. The total flow energy loss deviates significantly from the 1/7 power law equation when the relative flow depth is shallow. Both the coupled model and experiments indicate non-negligible subsurface flow that accounts for a considerable proportion of the total flow. By including the subsurface flow, the coupled model is able to predict a wider range of velocity profiles and total flow energy loss coefficients when compared with existing equations.

Erythropoietic bone marrow in the pigeon: Development of its distribution and volume during growth and pneumatization of bones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schepelmann, K.

1990-01-01

During postnatal development of the pigeon, a large portion of the skeleton becomes pneumatized, displacing the hemopoietic bone marrow. The consequences of pneumatization on distribution and quantity of bone marrow as well as the availability of other sites for hemopoiesis have been investigated. Hemopoietic marrow of differently aged pigeons divided into five groups from 1 week posthatching (p.h.) up to 6 months p.h. was labeled with Fe-59 and examined by serial whole-body sections. Autoradiography and morphometry as well as scintillation counts of single bones and organs were also carried out. No sign of a reactivation of embryonic sites of erythropoiesismore » was found. Bone marrow weight and its proportion of whole-body weight increased during the first 4 weeks p.h. from 0.54% to 2.44% and decreased in the following months to about 1.0%. The developing bone marrow showed a progressive distribution during the first months of life, eventually being distributed proportionally over the entire skeleton, except for the skull. At the age of 6 months p.h. bone marrow had been displaced, its volume decreasing in correlation to increasing pneumaticity and conversion to fatty marrow. This generates the characteristic pattern of bone marrow distribution in adult pigeons, which shows hemopoietic bone marrow in ulna, radius, femur, tibiotarsus, scapula, furcula, and the caudal vertebrae.« less

Quantitative MRI and spectroscopy of bone marrow

PubMed Central

Ruschke, Stefan; Dieckmeyer, Michael; Diefenbach, Maximilian; Franz, Daniela; Gersing, Alexandra S.; Krug, Roland; Baum, Thomas

2017-01-01

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332–353. PMID:28570033

TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function

NASA Technical Reports Server (NTRS)

Lu, L.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

2001-01-01

BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle fabrication and after growth factor release. At an optimal TGF-beta1 dosage of 1.0 ng/ml after 3 days, the released TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells over 21 days of culture, with increased total cell number, alkaline phosphatase activity, and osteocalcin production. CONCLUSIONS: PLGA/PEG blend microparticles can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor enhances marrow stromal cell proliferation and osteoblastic differentiation in vitro. CLINICAL RELEVANCE: Controlled release of TGF-beta1 from PLGA/PEG microparticles is representative of emerging tissue engineering technologies that may modulate cellular responses to encourage bone regeneration at a skeletal defect site.

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.

PET/CT versus bone marrow biopsy in the initial evaluation of bone marrow infiltration in various pediatric malignancies.

PubMed

Zapata, Claudia P; Cuglievan, Branko; Zapata, Catalina M; Olavarrieta, Raquel; Raskin, Scott; Desai, Kavita; De Angulo, Guillermo

2018-02-01

Accurate staging is essential in the prognosis and management of pediatric malignancies. Current protocols require screening for marrow infiltration with bone marrow biopsy (BMB) as the gold standard. Positron emission tomography-computed tomography (PET-CT) is commonly used to complete the staging process and can also be used to evaluate marrow infiltration. To compare PET-CT and BMB in the initial evaluation of bone marrow infiltration in pediatric cancers. We retrospectively reviewed new cases of EWS, rhabdomyosarcoma, neuroblastoma, and lymphoma diagnosed between January 2009 and October 2014. Each case had undergone both PET-CT and BMB within 4 weeks without treatment in the interval between screening modalities. We reviewed 69 cases. Bone marrow infiltration was demonstrated in 34 cases by PET-CT and in 18 cases by BMB. The sensitivity and negative predictive value of PET-CT were both 100%. Interestingly, the cases in which infiltration was not detected on BMB had an abnormal marrow signal on PET-CT focal or distant to iliac crest. PET-CT has a high sensitivity when assessing marrow infiltration in pediatric malignancies. Advances in radiologic modalities may obviate the use of invasive, painful, and costly procedures like BMB. Furthermore, biopsy results are limited by insufficient tissue or the degree of marrow infiltration (diffuse vs. focal disease). PET-CT can improve the precision of biopsy when used as a guiding tool. This study proposes the use of PET-CT as first-line screening for bone marrow infiltration to improve the accuracy of staging in new diagnoses. © 2017 Wiley Periodicals, Inc.

The role of bone marrow evaluation in the staging of patients with otherwise localized, low-risk neuroblastoma.

PubMed

Russell, Heidi V; Golding, Laurie A; Suell, Mary Nell; Nuchtern, Jed G; Strother, Douglas R

2005-12-01

Bone marrow aspirations and biopsies are standard staging procedures for neuroblastoma because the tumor frequently metastasizes to the bone marrow. The presence of bone marrow metastases indicates stage 4 or 4S neuroblastoma by International Neuroblastoma Staging System (INSS) criteria; these stages are also associated with other metastatic sites of disease. We questioned whether bone marrow studies changed the staging or treatment of children with localized, completely resected tumors if there was no other evidence of metastatic spread. If stage of disease rarely changed with bone marrow results, it might be possible to avoid this procedure in a subset of patients with neuroblastoma. The staging studies of patients with INSS stage 1 (n = 29), 4 (n = 60), and 4S (n = 13) neuroblastoma from two institutions were reviewed. There were no patients upstaged from stage 1 to 4 or 4S by bone marrow metastases alone. Fifty-nine of 60 stage 4 patients had other sites of metastases on imaging studies, the remaining patient had an unresectable primary tumor and marrow disease. All subjects with stage 4S disease had liver metastases. Bone marrow studies did not contribute data that changed the stage of patients who had surgically resectable tumors and no evidence of metastatic spread on imaging studies. When present, metastatic spread to the marrow was associated with advanced local tumors or other sites of metastatic disease. Given the relatively small size of our study population, further studies are warranted that investigate the utility of bone marrow studies for patients who otherwise have INSS stage 1 neuroblastoma. 2005 Wiley-Liss, Inc.

Aspiration and Biopsy: Bone Marrow

MedlinePlus

... Print What It Is Bone marrow aspirations and biopsies are performed to examine bone marrow, the spongy liquid part of the bone where blood cells are ... you might also feel the pressure of the biopsy needle pushing in. Some ... sharp cramp as the liquid bone marrow is withdrawn for the aspiration or ...

Appraisal of salinity and fluoride in a semi-arid region of India using statistical and multivariate techniques.

PubMed

Mor, Suman; Singh, Surender; Yadav, Poonam; Rani, Versha; Rani, Pushpa; Sheoran, Monika; Singh, Gurmeet; Ravindra, Khaiwal

2009-12-01

Various physico-chemical parameters, including fluoride (F(-)), were analyzed to understand the hydro-geochemistry of an aquifer in a semi-arid region of India. Furthermore, the quality of the shallow and deep aquifer (using tube well and hand pumps) was also investigated for their best ecological use including drinking, domestic, agricultural and other activities. Different multivariate techniques were applied to understand the groundwater chemistry of the aquifer. Findings of the correlation matrix were strengthened by the factor analysis, and this shows that salinity is mainly caused by magnesium salts as compared to calcium salts in the aquifer. The problem of salinization seems mainly compounded by the contamination of the shallow aquifers by the recharging water. High factor loading of total alkalinity and bicarbonates indicates that total alkalinity was mainly due to carbonates and bicarbonates of sodium. The concentration of F(-) was found more in the deep aquifer than the shallow aquifer. Further, only a few groundwater samples lie below the permissible limit of F(-), and this indicates a risk of dental caries in the populace of the study area. The present study indicates that regular monitoring of groundwater is an important step to avoid human health risks and to assess its quality for various ecological purposes.

[Deep needling and shallow needling at three acupoints around ear for subjective tinnitus: a randomized controlled trial].

PubMed

Yin, Tao; Ni, Jinxia; Zhu, Wenzeng

2015-10-01

To compare the effective differences between deep needling and shallow needling at three acupoints around ear for subjective tinnitus. Fifty patients with subjective tinnitus were randomized divided into a deep needling group and a shallow needling group, 25 cases in each group. Twenty-two patients in the deep needling group and 20 patients in the shallow needling group were brought into statistic in the end. In the two groups, the three acupoints around ear and distal acupoints were both selected. The acupoints of the affected side such as Yifeng (TE 17), Tinghui (GB 2), Ermen (TE 21), Zhigou (TE 6), Zhongzhu (TE 3) and Hegu (LI 4) were adopted. Yifeng (TE 17), Tinghui (GB 2) and Ermen (TE 21) were acupunctured 30-38 mm in the deep needling group and 15-20 mm in the shallow needling group. The other acupoints were conventionally acupunctured in the two groups. The needles were retained for 30 min,once a day and five times a week for all patients. The treatment was continuously for 4 weeks in the two groups. Tinnitus handicap inventory (THI) scores, tinnitus grades and visual analogue scale (VAS) for tinnitus sound levels were observed before and after treatment, and the effects of the two groups were compared. The total effective rate in the deep needling group was 59.1% (13/22), and it was better than 20.0% (4/20) in the shallow needling group (P < 0.05). In the deep needling, group, the THI score, tinnitus grade and the VAS score were improved than those before treatment (all P < 0.05). In the shallow needling group, the three above indices before and after treatment were not different in statistical significance (all P > 0.05). After treatment, all the three indices in the deep needling group were superior to those in the shallow needling group (all P < 0.05). Acupuncture at the three acupoints around ear deeply could apparently improve tinnitus, and reduce tinnitus sound levels for subjective tinnitus. The effect is better than that by shallow needling at the three acupoints.

Combined effects of climate change and bank stabilization on shallow water habitats of chinook salmon.

PubMed

Jorgensen, Jeffrey C; McClure, Michelle M; Sheer, Mindi B; Munn, Nancy L

2013-12-01

Significant challenges remain in the ability to estimate habitat change under the combined effects of natural variability, climate change, and human activity. We examined anticipated effects on shallow water over low-sloped beaches to these combined effects in the lower Willamette River, Oregon, an area highly altered by development. A proposal to stabilize some shoreline with large rocks (riprap) would alter shallow water areas, an important habitat for threatened Chinook salmon (Oncorhynchus tshawytscha), and would be subject to U.S. Endangered Species Act-mandated oversight. In the mainstem, subyearling Chinook salmon appear to preferentially occupy these areas, which fluctuate with river stages. We estimated effects with a geospatial model and projections of future river flows. Recent (1999-2009) median river stages during peak subyearling occupancy (April-June) maximized beach shallow water area in the lower mainstem. Upstream shallow water area was maximized at lower river stages than have occurred recently. Higher river stages in April-June, resulting from increased flows predicted for the 2080s, decreased beach shallow water area 17-32%. On the basis of projected 2080s flows, more than 15% of beach shallow water area was displaced by the riprap. Beach shallow water area lost to riprap represented up to 1.6% of the total from the mouth to 12.9 km upstream. Reductions in shallow water area could restrict salmon feeding, resting, and refuge from predators and potentially reduce opportunities for the expression of the full range of life-history strategies. Although climate change analyses provided useful information, detailed analyses are prohibitive at the project scale for the multitude of small projects reviewed annually. The benefits of our approach to resource managers include a wider geographic context for reviewing similar small projects in concert with climate change, an approach to analyze cumulative effects of similar actions, and estimation of the actions' long-term effects. Efectos Combinados del Cambio Climático y la Estabilización de Bordes de Ríos Hábitats de Aguas Poco Profundas del Salmón Chinook. Conservation Biology © 2013 Society for Conservation Biology No claim to original US government works.

Bone marrow edema in the knee in osteoarthrosis and association with total knee arthroplasty within a three-year follow-up

PubMed Central

Craig, Joseph; Nelson, Fred

2008-01-01

Objective The purpose of this study was to determine if a correlation exists between magnetic resonance imaging (MRI) findings of bone marrow edema (BME) in osteoarthrosis (OA) of the knee joint and need for total knee arthroplasty (TKA) within a follow-up period of 3 years. Materials and methods The entire database of knee MR studies over a 3-year period was used to select individuals with knee OA. A chart review was conducted to identify and include only those who had a 3-year follow-up appointment from the time of the initial MR study. There were 25 patients in the OA-only group (four men and 21 women; age range, 28–75; average age, 49.3 years). The OA and BME group had 48 patients (23 men and 25 women; average age, 55.5 years). The MRs were reviewed and interpreted by a musculoskeletal radiologist and were classified into one of four patterns of BME: none, focal, global, or cystic pattern. Meniscal tear and degree of cartilage loss were also assessed. Results Subjects who had BME of any pattern type were 8.95 times as likely to progress rapidly to a TKA when compared to subjects with no BME (p = 0.016). Subjects with a global pattern of BME were 5.45 times as likely to have a TKA compared to subjects with focal, cyst, or no BME (p < 0.05). Subjects with a global edema pattern were 13.04 times as likely to have a TKA than subjects with no marrow edema in the knee (p < 0.01). There was no correlation of TKA with meniscal tear or cartilage loss. The group of subjects who had a TKA were 12.6 years older than those who did not have a TKA (p < 0.001). However, the BME results were still significant after accounting for the age difference. Conclusion Our classification of patterns into global, focal, cystic, and absence of BME is an attempt to further define edema in osteoarthrosis and how it relates to clinical progression. Patients with BME and OA have an increased risk of TKA as opposed to OA and no marrow edema. The BME pattern with the worst prognosis for the knee is the global pattern. PMID:18463865

Unsteady viscous calculations of supersonic flows past deep and shallow three-dimensional cavities

NASA Technical Reports Server (NTRS)

Baysal, O.; Srinivasan, S.; Stallings, R. L.

1988-01-01

Computational simulations were performed for supersonic, turbulent flows over deep and shallow three-dimensional cavities. The width and the depth of these cavities were fixed at 2.5 in. and 0.5 in., respectively. Length-to-depth ratio of the deep cavity was 6 and that of the shallow cavity was 16. Freestream values of Mach number and Reynolds number were 1.50 and 2.0 x 10 to the 6th/ft., respectively, at a total temperature of 585 R. The thickness of the turbulent boundary layer at the front lip of the cavity was 0.2 in. Simulations of these oscillatory flows were generated through time-accurate solutions of Reynolds-averaged full Navier-Stokes equations using the explicit MacCormack scheme. The solutions are validated through comparisons with experimental data. The features of open and closed cavity flows and effects of the third dimension are illustrated through computational graphics.

Mini 3D for shallow gas reconnaissance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vallieres, T. des; Enns, D.; Kuehn, H.

1996-12-31

The Mini 3D project was undertaken by TOTAL and ELF with the support of CEPM (Comite d`Etudes Petrolieres et Marines) to define an economical method of obtaining 3D seismic HR data for shallow gas assessment. An experimental 3D survey was carried out with classical site survey techniques in the North Sea. From these data 19 simulations, were produced to compare different acquisition geometries ranging from dual, 600 m long cables to a single receiver. Results show that short offset, low fold and very simple streamer positioning are sufficient to give a reliable 3D image of gas charged bodies. The 3Dmore » data allow a much more accurate risk delineation than 2D HR data. Moreover on financial grounds Mini-3D is comparable in cost to a classical HR 2D survey. In view of these results, such HR 3D should now be the standard for shallow gas surveying.« less

Bathymetric mapping of shallow water surrounding Dongsha Island using QuickBird image

NASA Astrophysics Data System (ADS)

Li, Dongling; Zhang, Huaguo; Lou, Xiulin

2018-03-01

This article presents an experiment of water depth inversion using the band ratio method in Dongsha Island shallow water. The remote sensing data is from QuickBird satellite on April 19, 2004. The bathymetry result shows an extensive agreement with the charted depths. 129 points from the chart depth data were chosen to evaluate the accuracy of the inversion depth. The results show that when the water depth is less than 20m, the inversion depth is accord with the chart, while the water depth is more than 20m, the inversion depth is still among 15- 25m. Therefore, the remote sensing methods can only be effective with the inversion of 20m in Dongsha Island shallow water, rather than in deep water area. The total of 109 depth points less than 20m were used to evaluate the accuracy, the root mean square error is 2.2m.

A major QTL controlling deep rooting on rice chromosome 4

PubMed Central

Uga, Yusaku; Yamamoto, Eiji; Kanno, Noriko; Kawai, Sawako; Mizubayashi, Tatsumi; Fukuoka, Shuichi

2013-01-01

Drought is the most serious abiotic stress that hinders rice production under rainfed conditions. Breeding for deep rooting is a promising strategy to improve the root system architecture in shallow-rooting rice cultivars to avoid drought stress. We analysed the quantitative trait loci (QTLs) for the ratio of deep rooting (RDR) in three F2 mapping populations derived from crosses between each of three shallow-rooting varieties (‘ARC5955', ‘Pinulupot1', and ‘Tupa729') and a deep-rooting variety, ‘Kinandang Patong'. In total, we detected five RDR QTLs on chromosomes 2, 4, and 6. In all three populations, QTLs on chromosome 4 were found to be located at similar positions; they explained from 32.0% to 56.6% of the total RDR phenotypic variance. This suggests that one or more key genetic factors controlling the root growth angle in rice is located in this region of chromosome 4. PMID:24154623

A major QTL controlling deep rooting on rice chromosome 4.

PubMed

Uga, Yusaku; Yamamoto, Eiji; Kanno, Noriko; Kawai, Sawako; Mizubayashi, Tatsumi; Fukuoka, Shuichi

2013-10-24

Drought is the most serious abiotic stress that hinders rice production under rainfed conditions. Breeding for deep rooting is a promising strategy to improve the root system architecture in shallow-rooting rice cultivars to avoid drought stress. We analysed the quantitative trait loci (QTLs) for the ratio of deep rooting (RDR) in three F₂ mapping populations derived from crosses between each of three shallow-rooting varieties ('ARC5955', 'Pinulupot1', and 'Tupa729') and a deep-rooting variety, 'Kinandang Patong'. In total, we detected five RDR QTLs on chromosomes 2, 4, and 6. In all three populations, QTLs on chromosome 4 were found to be located at similar positions; they explained from 32.0% to 56.6% of the total RDR phenotypic variance. This suggests that one or more key genetic factors controlling the root growth angle in rice is located in this region of chromosome 4.

Microbial activity of trench leachates from shallow-land, low-level radioactive waste disposal sites.

PubMed Central

Francis, A J; Dobbs, S; Nine, B J

1980-01-01

Trench leachate samples collected anoxically from shallow-land, low-level radioactive waste disposal sites were analyzed for total aerobic and anaerobic populations, sulfate reducers, denitrifiers, and methanogens. Among the several aerobic and anaerobic bacteria isolated, only Bacillus sp., Pseudomonas sp., Citrobacter sp., and Clostridium sp. were identified. Mixed bacterial cultures isolated from the trench leachates were able to grow anaerobically in trench leachates, which indicates that the radionuclides and organic chemicals present were not toxic to these bacteria. Changes in concentrations of several of the organic constituents of the waste leachate samples were observed due to anaerobic microbial activity. Growth of a mixed culture of trench-water bacteria in media containing a mixture of radionuclides, 60Co, 85Sr, and 134,137Cs, was not affected at total activity concentrations of 2.6 X 10(2) and 2.7 X 10(3) pCi/ml. PMID:7406490

Comparison of Uncultured Marrow Mononuclear Cells and Culture-Expanded Mesenchymal Stem Cells in 3D Collagen-Chitosan Microbeads for Orthopedic Tissue Engineering

PubMed Central

Wise, Joel K.; Alford, Andrea I.; Goldstein, Steven A.

2014-01-01

Stem cell-based therapies have shown promise in enhancing repair of bone and cartilage. Marrow-derived mesenchymal stem cells (MSC) are typically expanded in vitro to increase cell number, but this process is lengthy, costly, and there is a risk of contamination and altered cellular properties. Potential advantages of using fresh uncultured bone marrow mononuclear cells (BMMC) include heterotypic cell and paracrine interactions between MSC and other marrow-derived cells including hematopoietic, endothelial, and other progenitor cells. In the present study, we compared the osteogenic and chondrogenic potential of freshly isolated BMMC to that of cultured-expanded MSC, when encapsulated in three-dimensional (3D) collagen-chitosan microbeads. The effect of low and high oxygen tension on cell function and differentiation into orthopedic lineages was also examined. Freshly isolated rat BMMC (25×106 cells/mL, containing an estimated 5×104 MSC/mL) or purified and culture-expanded rat bone marrow-derived MSC (2×105 cells/mL) were added to a 65–35 wt% collagen-chitosan hydrogel mixture and fabricated into 3D microbeads by emulsification and thermal gelation. Microbeads were cultured in control MSC growth media in either 20% O2 (normoxia) or 5% O2 (hypoxia) for an initial 3 days, and then in control, osteogenic, or chondrogenic media for an additional 21 days. Microbead preparations were evaluated for viability, total DNA content, calcium deposition, and osteocalcin and sulfated glycosaminoglycan expression, and they were examined histologically. Hypoxia enhanced initial progenitor cell survival in fresh BMMC-microbeads, but it did not enhance osteogenic potential. Fresh uncultured BMMC-microbeads showed a similar degree of osteogenesis as culture-expanded MSC-microbeads, even though they initially contained only 1/10th the number of MSC. Chondrogenic differentiation was not strongly supported in any of the microbead formulations. This study demonstrates the microbead-based approach to culturing and delivering cells for tissue regeneration, and suggests that fresh BMMC may be an alternative to using culture-expanded MSC for bone tissue engineering. PMID:23879621

Alpha imaging confirmed efficient targeting of CD45-positive cells after astatine-211 (211At)-radioimmunotherapy for hematopoietic cell transplantation

PubMed Central

Frost, Sofia H.L.; Miller, Brian W.; Bäck, Tom A.; Santos, Erlinda B.; Hamlin, Donald K.; Knoblaugh, Sue E.; Frayo, Shani L.; Kenoyer, Aimee L.; Storb, Rainer; Press, Oliver W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, Brenda M.

2015-01-01

Alpha-radioimmunotherapy targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-211 (211At)-radioimmunotherapy, extending the analysis to include intra-organ 211At activity distribution and α-imaging-based small-scale dosimetry, along with immunohistochemical staining. Methods Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of 211At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours post injection (p.i.), and six received autologous HCT three days after 211At-radioimmunotherapy, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. 211At localization and small-scale dosimetry were assessed using two α-imaging systems: α-camera and iQID. Results Uptake of 211At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted 211At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.1, 2.4, and 3.4 Gy/166 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion 211At-anti-CD45 radioimmunotherapy with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient 211At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT. PMID:26338894

Comparison of uncultured marrow mononuclear cells and culture-expanded mesenchymal stem cells in 3D collagen-chitosan microbeads for orthopedic tissue engineering.

PubMed

Wise, Joel K; Alford, Andrea I; Goldstein, Steven A; Stegemann, Jan P

2014-01-01

Stem cell-based therapies have shown promise in enhancing repair of bone and cartilage. Marrow-derived mesenchymal stem cells (MSC) are typically expanded in vitro to increase cell number, but this process is lengthy, costly, and there is a risk of contamination and altered cellular properties. Potential advantages of using fresh uncultured bone marrow mononuclear cells (BMMC) include heterotypic cell and paracrine interactions between MSC and other marrow-derived cells including hematopoietic, endothelial, and other progenitor cells. In the present study, we compared the osteogenic and chondrogenic potential of freshly isolated BMMC to that of cultured-expanded MSC, when encapsulated in three-dimensional (3D) collagen-chitosan microbeads. The effect of low and high oxygen tension on cell function and differentiation into orthopedic lineages was also examined. Freshly isolated rat BMMC (25 × 10(6) cells/mL, containing an estimated 5 × 10(4) MSC/mL) or purified and culture-expanded rat bone marrow-derived MSC (2 × 10(5) cells/mL) were added to a 65-35 wt% collagen-chitosan hydrogel mixture and fabricated into 3D microbeads by emulsification and thermal gelation. Microbeads were cultured in control MSC growth media in either 20% O2 (normoxia) or 5% O2 (hypoxia) for an initial 3 days, and then in control, osteogenic, or chondrogenic media for an additional 21 days. Microbead preparations were evaluated for viability, total DNA content, calcium deposition, and osteocalcin and sulfated glycosaminoglycan expression, and they were examined histologically. Hypoxia enhanced initial progenitor cell survival in fresh BMMC-microbeads, but it did not enhance osteogenic potential. Fresh uncultured BMMC-microbeads showed a similar degree of osteogenesis as culture-expanded MSC-microbeads, even though they initially contained only 1/10th the number of MSC. Chondrogenic differentiation was not strongly supported in any of the microbead formulations. This study demonstrates the microbead-based approach to culturing and delivering cells for tissue regeneration, and suggests that fresh BMMC may be an alternative to using culture-expanded MSC for bone tissue engineering.

Bone marrow monosomy 7: hematologic and clinical manifestations in childhood and adolescence.

PubMed

Hutter, J J; Hecht, F; Kaiser-McCaw, B; Hays, T; Baranko, P; Cohen, J; Durie, B

1984-01-01

The hematologic manifestations and clinical course are described for six children and adolescents with bone marrow monosomy 7. One child with secondary acute myelogenous leukemia had monosomy 7 plus a marker chromosome; the remaining patients had marrow monosomy 7 as the only karyotypic abnormality. The hematologic abnormalities were diverse, but the majority of patients had a smoldering preleukemic or myeloproliferative phase. Leukemic blasts were either undifferentiated or demonstrated evidence of myeloid differentiation. All patients responded poorly to antileukemic therapy. Bone marrow monosomy 7 was observed in one patient with severe marrow hypoplasia. Antileukemic therapy in another patient with greater than 30 per cent marrow blasts was associated with the development of a bone marrow myeloproliferative disorder with persistence of the monosomy 7 karyotype. We speculate that monosomy 7 may be a specific marker for a pluripotent hematopoietic stem cell abnormality that is associated with either blastic leukemia or a myeloproliferative disorder.

[Hypoplastic acute promyelocytic leukemia with continuous hypocellular bone marrow after remission].

PubMed

Nakamura, Toshiki; Makiyama, Junya; Matsuura, Ayumi; Kurohama, Hirokazu; Kitanosono, Hideaki; Ito, Masahiro; Yoshida, Shinichiro; Miyazaki, Yasushi

2018-01-01

An 87-year old female presented with unsteady gait and occasional subcutaneous hematomas. Blood examination findings revealed pancytopenia and mild coagulopathy. Both the histopathological evaluation of bone marrow smears and bone marrow biopsy revealed a hypocellular bone marrow. However, APL cells were observed and PML-RARA fusion gene was detected. On the basis of these findings, the patient was diagnosed with hypoplastic acute promyelocytic leukemia. She received ATRA treatment and achieved complete remission (CR) 29 days from the commencement of therapy. After the first CR, she received two courses of ATO as a consolidation therapy. Following the latter treatments, she maintained CR, but a hypoplastic bone marrow was still observed. Hypoplastic AML is defined as AML with a low bone marrow cellularity. It is clinically important to distinguish it from aplastic anemia and hypoplastic MDS. It has been suggested that both cytogenetic and morphological diagnosis are imperative to the differential diagnosis of hypocellular bone marrow.

Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine.

PubMed

Li, Guanqun; Liu, Xujun; Du, Qian; Gao, Mei; An, Jing

2015-08-01

The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. © 2015 by the Society for Experimental Biology and Medicine.

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

USDA-ARS?s Scientific Manuscript database

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...

Oral Microbiome of Deep and Shallow Dental Pockets In Chronic Periodontitis

PubMed Central

Ge, Xiuchun; Rodriguez, Rafael; Trinh, My; Gunsolley, John; Xu, Ping

2013-01-01

We examined the subgingival bacterial biodiversity in untreated chronic periodontitis patients by sequencing 16S rRNA genes. The primary purpose of the study was to compare the oral microbiome in deep (diseased) and shallow (healthy) sites. A secondary purpose was to evaluate the influences of smoking, race and dental caries on this relationship. A total of 88 subjects from two clinics were recruited. Paired subgingival plaque samples were taken from each subject, one from a probing site depth >5 mm (deep site) and the other from a probing site depth ≤3mm (shallow site). A universal primer set was designed to amplify the V4–V6 region for oral microbial 16S rRNA sequences. Differences in genera and species attributable to deep and shallow sites were determined by statistical analysis using a two-part model and false discovery rate. Fifty-one of 170 genera and 200 of 746 species were found significantly different in abundances between shallow and deep sites. Besides previously identified periodontal disease-associated bacterial species, additional species were found markedly changed in diseased sites. Cluster analysis revealed that the microbiome difference between deep and shallow sites was influenced by patient-level effects such as clinic location, race and smoking. The differences between clinic locations may be influenced by racial distribution, in that all of the African Americans subjects were seen at the same clinic. Our results suggested that there were influences from the microbiome for caries and periodontal disease and these influences are independent. PMID:23762384

Natural and anthropogenic factors affecting the shallow groundwater quality in a typical irrigation area with reclaimed water, North China Plain.

PubMed

Gu, Xiaomin; Xiao, Yong; Yin, Shiyang; Pan, Xingyao; Niu, Yong; Shao, Jingli; Cui, Yali; Zhang, Qiulan; Hao, Qichen

2017-09-22

In this study, the hydrochemical characteristics of shallow groundwater were analyzed to get insight into the factors affecting groundwater quality in a typical agricultural dominated area of the North China Plain. Forty-four shallow groundwater samples were collected for chemical analysis. The water type changes from Ca·Na-HCO 3 type in grass land to Ca·Na-Cl (+NO 3 ) type and Na (Ca)-Cl (+NO 3 +SO 4 ) type in construction and facility agricultural land, indicating the influence of human activities. The factor analysis and geostatistical analysis revealed that the two major factors contributing to the groundwater hydrochemical compositions were the water-rock interaction and contamination from sewage discharge and agricultural fertilizers. The major ions (F, HCO 3 ) and trace element (As) in the shallow groundwater represented the natural origin, while the nitrate and sulfate concentrations were related to the application of fertilizer and sewage discharge in the facility agricultural area, which was mainly affected by the human activities. The values of pH, total dissolved solids, electric conductivity, and conventional component (K, Ca, Na, Mg, Cl) in shallow groundwater increased from grass land and cultivated land, to construction land and to facility agriculture which were originated from the combination sources of natural processes (e.g., water-rock interaction) and human activities (e.g., domestic effluents). The study indicated that both natural processes and human activities had influences on the groundwater hydrochemical compositions in shallow groundwater, while anthropogenic processes had more contribution, especially in the reclaimed water irrigation area.

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.

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

Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease.

PubMed

Bueno, Clara; Roldan, Mar; Anguita, Eduardo; Romero-Moya, Damia; Martín-Antonio, Beatriz; Rosu-Myles, Michael; del Cañizo, Consuelo; Campos, Francisco; García, Regina; Gómez-Casares, Maite; Fuster, Jose Luis; Jurado, Manuel; Delgado, Mario; Menendez, Pablo

2014-07-01

Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease. Copyright© Ferrata Storti Foundation.

A method to generate enhanced GFP+ chimeric mice to study the role of bone marrow-derived cells in the eye.

PubMed

Singh, Vivek; Jaini, Ritika; Torricelli, André A M; Tuohy, Vincent K; Wilson, Steven E

2013-11-01

GFP-chimeric mice are important tools to study the role of bone marrow-derived cells in eye physiology. A method is described to generate GFP-chimeric mice using whole-body, sub-lethal radiation (600 rad) of wild-type C57BL/6 recipients followed by tail vein injection of bone marrow cells derived from GFP+ (GFP-transgenic C57/BL/6-Tg(UBC-GFP)30 Scha/J) mice. This method yields stable GFP+ chimeras with greater than 95% chimerism (range 95-99%), achieved within one month of bone marrow transfer confirmed by microscopy and fluorescence-assisted cell sorting (FACS) analysis, with lower mortality after irradiation than prior methods. To demonstrate the efficacy of GFP+ bone marrow chimeric mice, the role of circulating GFP+ bone marrow-derived cells in myofibroblast generation after irregular photo-therapeutic keratectomy (PTK) was analyzed. Many SMA+ myofibroblasts that were generated at one month after PTK were derived from GFP+ bone marrow-derived cells. The GFP+ bone marrow chimeric mouse provides an excellent model for studying the role of bone marrow-derived cells in corneal wound healing, glaucoma surgery, optic nerve head pathology and retinal pathophysiology and wound healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

PubMed

Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

2015-03-13

Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

Selective resistance of CD44hi T cells to p53-dependent cell death results in persistence of immunologic memory after total body irradiation.

PubMed

Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

2011-10-15

Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation markedly changes the balance of residual T cell subsets to favor CD4(+)CD44(hi) NKT cells because of the differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results showed that CD4(+) T cells were markedly more resistant than CD8(+) T cells, and CD44(hi) T cells, including NKT cells and memory T cells, were markedly more resistant than CD44(lo) (naive) T cells. The memory T cells immunized to alloantigens persisted even after myeloablative (1000 cGy) TBI and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1000 cGy was prevented in p53(-/-) mice, there was progressive T cell death in p53(-/-) mice at higher doses. Although p53-dependent T cell death changed the balance of subsets, p53-independent T cell death did not. In conclusion, resistance of CD44(hi) T cells to p53-dependent cell death results in the persistence of immunological memory after TBI and can explain the immune-mediated rejection of marrow transplants in sensitized recipients.

Shallow temperature differences along the Deep Creek Range front, Idaho

NASA Astrophysics Data System (ADS)

Ore, H. T.; Wiegand, G. H.

1990-02-01

The extent of the solvolysis reaction of a tertiary butyl chloride solution placed in vials buried about 1.2 m below the ground surface is dependent on average temperature at that depth over the period of burial. This method is herein used to indicate differences in shallow temperature from the western flank of the Basin and Range Deep Creek Range front, about 5 km westward into Rockland Valley in southeastern Idaho. Ninety-three samples, distributed to allow determination of lateral and vertical sample-site variation in total reaction amount, were analyzed after being in place for 3 months. Results from two sample lines, 3.5 km apart, show that subsurface total reaction amount declines slightly for the first 1.6 km away from the mountain front, rises abruptly to several times initial reaction, slowly declines for the next several km, then tends to slowly rise again. Plots of extent of reaction vs distance for the two traverses are nearly parallel; in both the abrupt increase in total reaction coincides with a line of springs, suggesting that hydrologic activity is at least related to the effects noted.

Persistent injury-associated anemia: the role of the bone marrow microenvironment.

PubMed

Millar, Jessica K; Kannan, Kolenkode B; Loftus, Tyler J; Alamo, Ines G; Plazas, Jessica; Efron, Philip A; Mohr, Alicia M

2017-06-15

The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β, interleukin-10, stem cell factor, transforming growth factor-β, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1β, interleukin-10, stem cell factor, and transforming growth factor-β) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Donor Experiences of Second Marrow or Peripheral Blood Stem Cell Collection Mirror the First, but CD34+ Yields Are Less.

PubMed

Stroncek, David F; Shaw, Bronwen E; Logan, Brent R; Kiefer, Deidre M; Savani, Bipin N; Anderlini, Paolo; Bredeson, Christopher N; Hematti, Peiman; Ganguly, Siddhartha; Diaz, Miguel Angel; Abdel-Azim, Hisham; Ahmed, Ibrahim; Maharaj, Dipnarine; Seftel, Matthew; Beitinjaneh, Amer; Seo, Sachiko; Yared, Jean A; Halter, Joerg; O'Donnell, Paul V; Hale, Gregory A; DeFilipp, Zachariah; Lazarus, Hillard; Liesveld, Jane L; Zhou, Zheng; Munshi, Pashna; Olsson, Richard F; Kasow, Kimberly Anne; Szer, Jeffrey; Switzer, Galen E; Chitphakdithai, Pintip; Shah, Nirali; Confer, Dennis L; Pulsipher, Michael A

2018-01-01

Little is known about the experiences of individuals donating peripheral blood stem cells (PBSCs) or marrow for a second time. To study this, unrelated donors making a second donation through the National Marrow Donor Program between 2004 and 2013 were evaluated. Experiences of second-time donors giving marrow (n = 118: first donation was PBSC in 76 and marrow in 42) were compared with those making only 1 marrow donation (n = 5829). Experiences of second-time donors giving PBSCs (n = 602) (first donation was PBSCs in 362; marrow in 240) were compared to first-time PBSC donors (n = 16,095). For donors giving a second PBSC or marrow donation there were no significant differences in maximum skeletal pain, maximum symptoms measured by an established modified toxicity criteria, and recovery time compared with those who donated only once. Notably, the yield of marrow nucleated cells and PBSC CD34 + cells with second donations was less. As previously noted with single first-time donations, female (PBSCs and marrow) and obese donors (PBSCs) had higher skeletal pain and/or toxicity with a second donation. PBSC donors who experienced high levels of pain or toxicity with the first donation also experienced high levels of these symptoms with their second donation and slower recovery times. In conclusion, for most donors second donation experiences were similar to first donation experiences, but CD34 + yields were less. Knowledge of the donor's first experience and stem cell yields may help centers decide whether second donations are appropriate and institute measures to improve donor experiences. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Reef Fish Community Biomass and Trophic Structure Changes across Shallow to Upper-Mesophotic Reefs in the Mesoamerican Barrier Reef, Caribbean

PubMed Central

Gress, Erika; Wright, Georgina; Exton, Dan A.; Rogers, Alex D.

2016-01-01

Mesophotic coral ecosystems (MCEs; reefs 30-150m depth) are of increased research interest because of their potential role as depth refuges from many shallow reef threats. Yet few studies have identified patterns in fish species composition and trophic group structure between MCEs and their shallow counterparts. Here we explore reef fish species and biomass distributions across shallow to upper-MCE Caribbean reef gradients (5-40m) around Utila, Honduras, using a diver-operated stereo-video system. Broadly, we found reef fish species richness, abundance and biomass declining with depth. At the trophic group level we identified declines in herbivores (both total and relative community biomass) with depth, mostly driven by declines in parrotfish (Scaridae). Piscivores increased as a proportion of the community with increased depth while, in contrast to previous studies, we found no change in relative planktivorous reef fish biomass across the depth gradient. In addition, we also found evidence of ontogenetic migrations in the blue tang (Acanthurus coeruleus), striped parrotfish (Scarus iserti), blue chromis (Chromis cyanea), creole wrasse (Clepticus parrae), bluehead wrasse (Thalassoma bifasciatum) and yellowtail snapper (Ocyurus chrysurus), with a higher proportion of larger individuals at mesophotic and near-mesophotic depths than on shallow reefs. Our results highlight the importance of using biomass measures when considering fish community changes across depth gradients, with biomass generating different results to simple abundance counts. PMID:27332811

SU-E-T-13: A Comparative Dosimetric Study On Radio-Dynamic Therapy for Pelvic Cancer Treatment: Strategies for Bone Marrow Dose and Volume Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, C; Renmin Hospital of Wuhan University, Wuhan, Hubei Province; Wang, B

Purpose: Radio-dynamic therapy (RDT) is a potentially effective modality for local and systemic cancer treatment. Using RDT, the administration of a radio-sensitizer enhances the biological effect of high-energy photons. Although the sensitizer uptake ratio of tumor to normal tissue is normally high, one cannot simply neglect its effect on critical structures. In this study, we aim to explore planning strategies to improve bone marrow sparing without compromising the plan quality for RDT treatment of pelvic cancers. Methods: Ten cervical and ten prostate cancer patients who previously received radiotherapy at our institution were selected for this study. For each patient, ninemore » plans were created using the Varian Eclipse treatmentplanning-system (TPS) with 3D-CRT, IMRT, and VMAT delivery techniques containing various gantry angle combinations and optimization parameters (dose constraints to the bone marrow). To evaluate the plans for bone marrow sparing, the dose-volume parameters V5, V10, V15, V20, V30, and V40 for bone marrow were examined. Effective doseenhancement factors for the sensitizer were used to weigh the dose-volume histograms for various tissues from individual fractions. Results: The planning strategies had different impacts on bone marrow sparing for the cervical and prostate cases. For the cervical cases, provided the bone marrow constraints were properly set during optimization, the dose to bone marrow sparing was found to be comparable between different IMRT and VMAT plans regardless of the gantry angle selection. For the prostate cases, however, careful selection of gantry angles could dramatically improve the bone marrow sparing, although the dose distribution in bone marrow was clinically acceptable for all prostate plans that we created. Conclusion: For intensity-modulated RDT planning for cervical cancer, planners should set bone marrow constraints properly to avoid any adverse damage, while for prostate cancer one can carefully select gantry angles to improve bone marrow sparing when necessary.« less

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

PubMed

Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

2017-01-01

Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

PubMed

Marachelian, Araz; Villablanca, Judith G; Liu, Cathy W; Liu, Betty; Goodarzian, Fariba; Lai, Hollie A; Shimada, Hiroyuki; Tran, Hung C; Parra, Jaime A; Gallego, Richard; Bedrossian, Nora; Young, Sabrina; Czarnecki, Scarlett; Kennedy, Rebekah; Weiss, Brian D; Goldsmith, Kelly; Granger, Meaghan; Matthay, Katherine K; Groshen, Susan; Asgharzadeh, Shahab; Sposto, Richard; Seeger, Robert C

2017-09-15

Purpose: We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. Experimental Design: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ C t , for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, 123 I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between Δ C t and progression-free survival (PFS). Results: NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their Δ C t values were correlated (Spearman r = 0.67, P < 0.0001), although bone marrow C t was 7.9 ± 0.5 C t stronger than blood C t When bone marrow morphology, MIBG, or CT/MRI were positive, NB-mRNA was detected in 99% (99/100), 88% (100/113), and 81% (82/101) of bone marrow samples. When all three were negative, NB-mRNA was detected in 55% (11/20) of bone marrow samples. Bone marrow NB-mRNA correlated with bone marrow morphology or MIBG positivity ( P < 0.0001 and P = 0.007). Bone marrow and blood Δ C t values correlated with PFS ( P < 0.001; P = 0.001) even when bone marrow was morphologically negative ( P = 0.001; P = 0.014). Multivariate analysis showed that bone marrow and blood Δ C t values were associated with PFS independently of clinical disease and MYCN gene status ( P < 0.001; P = 0.055). Conclusions: This five-gene NB5 assay for NB-mRNA improves definition of disease status and correlates independently with PFS in relapsed/refractory neuroblastoma. Clin Cancer Res; 23(18); 5374-83. ©2017 AACR . ©2017 American Association for Cancer Research.

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. Themore » methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm{sup 3} corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.« less

Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

PubMed

Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

2015-05-25

The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A STUDY OF PREDICTED BONE MARROW DISTRIBUTION ON CALCULATED MARROW DOSE FROM EXTERNAL RADIATION EXPOSURES USING TWO SETS OF IMAGE DATA FOR THE SAME INDIVIDUAL

PubMed Central

Caracappa, Peter F.; Chao, T. C. Ephraim; Xu, X. George

2010-01-01

Red bone marrow is among the tissues of the human body that are most sensitive to ionizing radiation, but red bone marrow cannot be distinguished from yellow bone marrow by normal radiographic means. When using a computational model of the body constructed from computed tomography (CT) images for radiation dose, assumptions must be applied to calculate the dose to the red bone marrow. This paper presents an analysis of two methods of calculating red bone marrow distribution: 1) a homogeneous mixture of red and yellow bone marrow throughout the skeleton, and 2) International Commission on Radiological Protection cellularity factors applied to each bone segment. A computational dose model was constructed from the CT image set of the Visible Human Project and compared to the VIP-Man model, which was derived from color photographs of the same individual. These two data sets for the same individual provide the unique opportunity to compare the methods applied to the CT-based model against the observed distribution of red bone marrow for that individual. The mass of red bone marrow in each bone segment was calculated using both methods. The effect of the different red bone marrow distributions was analyzed by calculating the red bone marrow dose using the EGS4 Monte Carlo code for parallel beams of monoenergetic photons over an energy range of 30 keV to 6 MeV, cylindrical (simplified CT) sources centered about the head and abdomen over an energy range of 30 keV to 1 MeV, and a whole-body electron irradiation treatment protocol for 3.9 MeV electrons. Applying the method with cellularity factors improves the average difference in the estimation of mass in each bone segment as compared to the mass in VIP-Man by 45% over the homogenous mixture method. Red bone marrow doses calculated by the two methods are similar for parallel photon beams at high energy (above about 200 keV), but differ by as much as 40% at lower energies. The calculated red bone marrow doses differ significantly for simplified CT and electron beam irradiation, since the computed red bone marrow dose is a strong function of the cellularity factor applied to bone segments within the primary radiation beam. These results demonstrate the importance of properly applying realistic cellularity factors to computation dose models of the human body. PMID:19430219

A study of predicted bone marrow distribution on calculated marrow dose from external radiation exposures using two sets of image data for the same individual.

PubMed

Caracappa, Peter F; Chao, T C Ephraim; Xu, X George

2009-06-01

Red bone marrow is among the tissues of the human body that are most sensitive to ionizing radiation, but red bone marrow cannot be distinguished from yellow bone marrow by normal radiographic means. When using a computational model of the body constructed from computed tomography (CT) images for radiation dose, assumptions must be applied to calculate the dose to the red bone marrow. This paper presents an analysis of two methods of calculating red bone marrow distribution: 1) a homogeneous mixture of red and yellow bone marrow throughout the skeleton, and 2) International Commission on Radiological Protection cellularity factors applied to each bone segment. A computational dose model was constructed from the CT image set of the Visible Human Project and compared to the VIP-Man model, which was derived from color photographs of the same individual. These two data sets for the same individual provide the unique opportunity to compare the methods applied to the CT-based model against the observed distribution of red bone marrow for that individual. The mass of red bone marrow in each bone segment was calculated using both methods. The effect of the different red bone marrow distributions was analyzed by calculating the red bone marrow dose using the EGS4 Monte Carlo code for parallel beams of monoenergetic photons over an energy range of 30 keV to 6 MeV, cylindrical (simplified CT) sources centered about the head and abdomen over an energy range of 30 keV to 1 MeV, and a whole-body electron irradiation treatment protocol for 3.9 MeV electrons. Applying the method with cellularity factors improves the average difference in the estimation of mass in each bone segment as compared to the mass in VIP-Man by 45% over the homogenous mixture method. Red bone marrow doses calculated by the two methods are similar for parallel photon beams at high energy (above about 200 keV), but differ by as much as 40% at lower energies. The calculated red bone marrow doses differ significantly for simplified CT and electron beam irradiation, since the computed red bone marrow dose is a strong function of the cellularity factor applied to bone segments within the primary radiation beam. These results demonstrate the importance of properly applying realistic cellularity factors to computation dose models of the human body.

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 - discharge; ...

Cocaine-contaminated allogeneic bone marrow transplantation.

PubMed

Keung, Y K; Morgan, D; Cobos, E

2001-01-01

Should a person with history of drug addiction be categorically denied as a bone marrow donor? The answer to the question is controversial. We report a case of allogeneic bone marrow transplantation for refractory acute myeloid leukemia preceded by essential thrombocythemia. The donor used cocaine and marijuana the night before the bone marrow harvest. Copyright 2001 S. Karger AG, Basel

SBDS Protein Expression Patterns in the Bone Marrow

PubMed Central

Wong, Trisha E.; Calicchio, Monica L.; Fleming, Mark D.; Shimamura, Akiko; Harris, Marian H.

2010-01-01

Shwachman Diamond Syndrome (SDS) is an inherited bone marrow failure syndrome caused by biallelic SBDS gene mutations. Here we examined SBDS protein levels in human bone marrow. SBDS protein expression was high in neutrophil progenitors, megakaryocytes, plasma cells and osteoblasts. In contrast, SBDS protein levels were low in all hematopoietic cell lineages from patients harboring the common SBDS mutations. We conclude that SBDS protein levels vary widely between specific marrow lineages. Uniformly low SBDS protein expression levels distinguish the majority of SDS patients from controls or other marrow failure syndromes. PMID:20658628

Amodiaquine induced agranulocytosis: inhibition of colony growth in bone marrow by antimalarial agents.

PubMed Central

Rhodes, E G; Ball, J; Franklin, I M

1986-01-01

Bone marrow was cultured in vitro for colonies of granulocytes and macrophages five months after a patient had recovered from amodiaquine induced agranulocytosis. The addition of amodiaquine, chloroquine, and sulfadoxine to the culture was followed by a dose dependent inhibition of colony growth in the patient's marrow but not in normal control bone marrow. Colony growth was, however, unaffected by proguanil, pyrimethamine, and quinine. These findings show that in vitro marrow culture may have important predictive value in some cases of drug induced agranulocytosis. PMID:3082409

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. © 2015 John Wiley & Sons Ltd.

Diminished Wastewater Treatment: Evaluation of Septic System Performance Under a Climate Change Scenario

NASA Astrophysics Data System (ADS)

Cooper, J.; Loomis, G.; Kalen, D.; Boving, T. B.; Morales, I.; Amador, J.

2015-12-01

The effects of climate change are expected to reduce the ability of soil-based onsite wastewater treatment systems (OWTS), to treat domestic wastewater. In the northeastern U.S., the projected increase in atmospheric temperature, elevation of water tables from rising sea levels, and heightened precipitation will reduce the volume of unsaturated soil and oxygen available for treatment. Incomplete removal of contaminants may lead to transport of pathogens, nutrients, and biochemical oxygen demand (BOD) to groundwater, increasing the risk to public health and likelihood of eutrophying aquatic ecosystems. Advanced OWTS, which include pre-treatment steps and provide unsaturated drainfields of greater volume relative to conventional OWTS, are expected to be more resilient to climate change. We used intact soil mesocosms to quantify water quality functions for two advanced shallow narrow drainfield types and a conventional drainfield under a current climate scenario and a moderate climate change scenario of 30 cm rise in water table and 5°C increase in soil temperature. While no fecal coliform bacteria (FCB) was released under the current climate scenario, up to 109 CFU FCB/mL (conventional) and up to 20 CFU FCB/mL (shallow narrow) were released under the climate change scenario. Total P removal rates dropped from 100% to 54% (conventional) and 71% (shallow narrow) under the climate change scenario. Total N removal averaged 17% under both climate scenarios in the conventional, but dropped from 5.4% to 0% in the shallow narrow under the climate change scenario, with additional leaching of N in excess of inputs indicating release of previously held N. No significant difference was observed between scenarios for BOD removal. The initial data indicate that while advanced OWTS retain more function under the climate change scenario, all three drainfield types experience some diminished treatment capacity.

Change in the size of Walker Lake during the past 5000 years

USGS Publications Warehouse

Benson, L.V.; Meyers, P.A.; Spencer, R.J.

1991-01-01

In 1984, a 12-m sediment core (WLC84-8) was taken from the deepest part of Walker Lake. Samples of the core were analysed for diatoms, pollen, carbonate mineralogy, magnesium content, ??18O and ??13C values of the total inorganic fractin, ??18O and ??13C values of Limnocythere ceriotuberosa, ??13C values of the total organic fraction, grain size, and magnetic susceptibility. The data indicate that Walker Lake became shallow and probably desiccated between ???5300-4800 and 2700-2100 yr B.P.. Each of the organic and inorganic proxy indicators of lake size discussed in this paper was useful in determining the presence of the shallow-lake intervals. However, none of the indicators was useful in determining the cause of the shallow-lake intervals. Instead, the types of fish living in Walker Lake prior to 1940 were used to demonstrate that shallow-lake intervals resulted from diversion of the Walker River and not from climatic aridity. Major changes in mineralogy and magnesium content of carbonates and major changes in diatom populations with time were found to be a function of the chemical evolution of Walker Lake combined with changing lake size. The stable isotopes of oxygen and carbon were found to be good indicators of lake volume changes. A lake-level record for Walker Lake constructed from stable-isotope data was found to be similar to a lake-level record constructed using tufa and tree-stump data. Both records indicate relatively high lake levels between 4800-2700 yr B.P., at 1250 yr B.P., and within the last 300 yr. Substantial declines in lake level occurred ???2000 and ???1000 yr B.P. ?? 1991.

Management of the Critically Ill Marrow Transplant Patient

DTIC Science & Technology

1988-01-01

dose-limiting factor diation (TBI) on serum amylase. Total serum amylase (21, 81). In addition, in allogeneic (non-self) was measured on 30 patients...refractory lo other Iherapy. By Polyclonal immune serum globulin (ISC) or nature of the production process, however. antilymphocyte immuioglobulin (ALG) anti...8217 .tients by giving CMV-negative blood products struction of lymphocytes. In severe cases, hy- and by avoiding the use of CMV-positive mar- potension

Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic

DTIC Science & Technology

2008-12-01

statistically significant. T. Chol indicates total cholesterol ; HDL, high - density lipoprotein . B, Hematoxylin and eosin staining of proximal aortas from...low density lipoprotein receptor null Ldlr/ mice transplanted with Stat1/ bone marrow. Conclusions—STAT1 is critical for endoplasmic reticulum...intracellular accumulation of lipoprotein - derived free cholesterol (FC).11 FC enrichment of macro- phages, like many ER stressors, activates the UPR

Dosimetry for radiobiological studies of the human hematopoietic system

NASA Technical Reports Server (NTRS)

Beck, W. L.; Stokes, T. R.; Lushbaugh, C. C.

1972-01-01

A system for estimating individual bone marrow doses in therapeutic radiation exposures of leukemia patients was studied. These measurements are used to make dose response correlations and to study the effect of dose protraction on peripheral blood cell levels. Three irradiators designed to produce a uniform field of high energy gamma radiation for total body exposures of large animals and man are also used for radiobiological studies.

Analysis of the Shallow Groundwater Flow System at Fire Island National Seashore, Suffolk County, New York

USGS Publications Warehouse

Schubert, Christopher E.

2010-01-01

Fire Island National Seashore (FIIS) occupies 42 kilometers of the barrier island for which it is named that lies off the southern shore of Suffolk County, N.Y. Freshwater in the highly permeable, sandy aquifer underlying Fire Island is bounded laterally by marine surface waters and at depth by saline groundwater. Interspersed throughout FIIS are 17 pre-existing residential communities that in summer months greatly increase in population through the arrival of summer residents and vacationers; in addition, the National Park Service (NPS) has established several facilities on the island to accommodate visitors to FIIS. The 2.2 million people estimated by the NPS to visit Fire Island annually impact groundwater quality through the release of waste-derived contaminants, such as nutrients, pathogens, and organic compounds, into the environment. Waste-contaminated groundwater can move through the aquifer and threaten the ecological health of the adjacent back-barrier estuaries to which much of the groundwater ultimately discharges. In 2004, the U.S. Geological Survey (USGS), in cooperation with the NPS, began a 3-year investigation to (1) collect groundwater levels and water-quality (nutrient) samples, (2) develop a three-dimensional model of the shallow (water-table) aquifer system and adjacent marine surface waters, and (3) calculate nitrogen loads in simulated groundwater discharges from the aquifer to back-barrier estuaries and the ocean. The hydrogeology of the shallow aquifer system was characterized from the results of exploratory drilling, geophysical surveying, water-level monitoring, and water-quality sampling. The investigation focused on four areas-the communities of Kismet and Robbins Rest, the NPS Visitor Center at Watch Hill, and the undeveloped Otis Pike Fire Island High Dune Wilderness. Thirty-five observation wells were installed within FIIS to characterize subsurface hydrogeology and establish a water-table monitoring network in the four study areas. A variable-density model of the shallow aquifer system and adjacent marine surface waters was developed to simulate groundwater flow patterns and rates. Nitrogen loads from the shallow aquifer system were calculated from representative total nitrogen (TN) concentrations and simulated groundwater discharges to back-barrier estuaries and the ocean. The model simulates groundwater directions, velocities, and discharge rates under 2005 mean annual conditions. Groundwater budgets were developed for recharge areas of similar land use that contribute freshwater to back-barrier estuaries, the ocean, and subsea-discharge zones. Total freshwater discharge from the shallow aquifer system is about 43,500 cubic meters per day (m3/d) (79.8 percent) to back-barrier estuaries and about 10,200 m3/d (18.7 percent) to the ocean; about 836 m3/d (1.5 percent) may exit the system as subsea underflow. The total contribution of fresh groundwater to shoreline discharge zones amounts to about 53,700 m3/d (98.5 percent). The median age of freshwater discharged to back-barrier estuaries and the ocean was 3.4 years, and the 95th-percentile age was 20 years. The TN concentrations and loads under 2005 mean annual conditions for areas that contribute fresh groundwater to back-barrier estuaries and the ocean were calculated for the principal land uses on Fire Island. The overall TN load from the shallow aquifer system to shoreline discharge zones is about 16,200 kilograms per year (kg/yr) (82.2 percent) to back-barrier estuaries and about 3,500 kg/yr (17.8 percent) to the ocean. The overall TN load to marine surface waters amounts to about 19,700 kg/yr-roughly 6 percent of the annual TN load from shallow groundwater entering the South Shore Estuary Reserve (SSER) from the Suffolk County mainland, which is about 345,000 kg/yr. In contrast to the TN load from shallow groundwater for the SSER watershed, which annually yields about 353 kilograms per square kilometer (kg/km2), the overall TN loa

Severe bone marrow edema on sacroiliac joint MRI increases the risk of low BMD in patients with axial spondyloarthritis.

PubMed

Kim, Ha Neul; Jung, Joon-Yong; Hong, Yeon Sik; Park, Sung-Hwan; Kang, Kwi Young

2016-03-02

To determine the association between inflammatory and structural lesions on sacroiliac joint (SIJ) MRI and BMD and to identify risk factors for low BMD in patients with axial spondyloarthritis (axSpA). Seventy-six patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI and BMD measurement at the lumbar spine, femoral neck, and total hip. Inflammatory and structural lesions on SIJ MRI were scored. Laboratory tests and assessment of radiographic and disease activity were performed at the time of MRI. The association between SIJ MRI findings and BMD was evaluated. Among the 76 patients, 14 (18%) had low BMD. Patients with low BMD showed significantly higher bone marrow edema (BME) and deep BME scores on MRI than those with normal BMD (p < 0.047 and 0.007, respectively). Inflammatory lesions on SIJ MRI correlated with BMD at the femoral neck and total hip. Multivariate analysis identified the presence of deep BME on SIJ MRI, increased CRP, and sacroiliitis on X-ray as risk factors for low BMD (OR = 5.6, 14.6, and 2.5, respectively). The presence of deep BME on SIJ MRI, increased CRP levels, and severity of sacroiliitis on X-ray were independent risk factors for low BMD.

Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

PubMed Central

Woodburn, Kathryn W.; Holmes, Christopher P.; Wilson, Susan D.; Fong, Kei-Lai; Press, Randall J.; Moriya, Yuu; Tagawa, Yoshihiko

2011-01-01

The pharmacokinetics(PK) (absorption, distribution, metabolism, excretion) of peginesatide.a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA), was evaluated in rats. The PK profile was evaluated at 0.1-5 mg·kg−1 IV using unlabeled or [14C]-labeled peginesatide. Mass balance, tissue distribution and metabolism were evaluated following IV administration of 5 mg·kg−1 [14C]-peginesatide, with tissue distribution also evaluated by quantitative whole-body autoradiography (QWBA) following an IV dose of 17 mg·kg−1[14C]-peginesatide. Plasma clearance was slow and elimination was biphasic with unchanged peginesatide representing >90% of the total radioactivity of the total radioactive exposure. Slow uptake of the radiolabeled compound from the vascular compartment into the tissues was observed. Biodistribution to bone marrow and extramedullary hematopoietic sites, and to highly vascularized lymphatic and excretory tissues occurred. A predominant degradation event to occur in vivo was the loss of one PEG chain from the branched PEG moiety to generate mono-PEG. Renal excretion was the primary mechanism (41%) of elimination, with parent molecule (67%) the major moiety excreted. In conclusion, elimination of [14C]-peginesatide-derived radioactivity was extended, retention preferentially occurred at sites of erythropoiesis (bone marrow), and urinary excretion was the primary elimination route. PMID:22188389

Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fermand, J.P.; Levy, Y.; Gerota, J.

1989-01-01

Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15more » and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.« less

Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

PubMed

Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

2009-12-15

The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice

PubMed Central

Pinheiro, Daphne; Leirós, Luana; Dáu, Juliana Barbosa Torreão; Stumbo, Ana Carolina; Thole, Alessandra Alves; Cortez, Erika Afonso Costa; Mandarim-de-Lacerda, Carlos Alberto; de Carvalho, Lais

2017-01-01

Bone marrow cells (BMC) migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation. Regarding total cell populations, there was a significant reduction in CD68+ cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver, related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-γ and HGF) and reduction of pro-inflammatory cytokines (IL-17A and IL-6). Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration. PMID:29176797

Groundwater-quality data in the Monterey–Salinas shallow aquifer study unit, 2013: Results from the California GAMA Program

USGS Publications Warehouse

Goldrath, Dara A.; Kulongoski, Justin T.; Davis, Tracy A.

2016-09-01

Groundwater quality in the 3,016-square-mile Monterey–Salinas Shallow Aquifer study unit was investigated by the U.S. Geological Survey (USGS) from October 2012 to May 2013 as part of the California State Water Resources Control Board Groundwater Ambient Monitoring and Assessment (GAMA) Program’s Priority Basin Project. The GAMA Monterey–Salinas Shallow Aquifer study was designed to provide a spatially unbiased assessment of untreated-groundwater quality in the shallow-aquifer systems in parts of Monterey and San Luis Obispo Counties and to facilitate statistically consistent comparisons of untreated-groundwater quality throughout California. The shallow-aquifer system in the Monterey–Salinas Shallow Aquifer study unit was defined as those parts of the aquifer system shallower than the perforated depth intervals of public-supply wells, which generally corresponds to the part of the aquifer system used by domestic wells. Groundwater quality in the shallow aquifers can differ from the quality in the deeper water-bearing zones; shallow groundwater can be more vulnerable to surficial contamination.Samples were collected from 170 sites that were selected by using a spatially distributed, randomized grid-based method. The study unit was divided into 4 study areas, each study area was divided into grid cells, and 1 well was sampled in each of the 100 grid cells (grid wells). The grid wells were domestic wells or wells with screen depths similar to those in nearby domestic wells. A greater spatial density of data was achieved in 2 of the study areas by dividing grid cells in those study areas into subcells, and in 70 subcells, samples were collected from exterior faucets at sites where there were domestic wells or wells with screen depths similar to those in nearby domestic wells (shallow-well tap sites).Field water-quality indicators (dissolved oxygen, water temperature, pH, and specific conductance) were measured, and samples for analysis of inorganic constituents (trace elements, nutrients, major and minor ions, silica, total dissolved solids, and alkalinity) were collected at all 170 sites. In addition to these constituents, the samples from grid wells were analyzed for organic constituents (volatile organic compounds, pesticides and pesticide degradates), constituents of special interest (perchlorate and N-nitrosodimethylamine, or NDMA), radioactive constituents (radon-222 and gross-alpha and gross-beta radioactivity), and geochemical and age-dating tracers (stable isotopes of carbon in dissolved inorganic carbon, carbon-14 abundances, stable isotopes of hydrogen and oxygen in water, and tritium activities).Three types of quality-control samples (blanks, replicates, and matrix spikes) were collected at up to 11 percent of the wells in the Monterey–Salinas Shallow Aquifer study unit, and the results for these samples were used to evaluate the quality of the data from the groundwater samples. With the exception of trace elements, blanks rarely contained detectable concentrations of any constituent, indicating that contamination from sample-collection procedures was not a significant source of bias in the data for the groundwater samples. Low concentrations of some trace elements were detected in blanks; therefore, the data were re-censored at higher reporting levels. Replicate samples generally were within the limits of acceptable analytical reproducibility. The median values of matrix-spike recoveries were within the acceptable range (70 to 130 percent) for the volatile organic compounds (VOCs) and N-nitrosodimethylamine (NDMA), but were only approximately 64 percent for pesticides and pesticide degradates.The sample-collection protocols used in this study were designed to obtain representative samples of groundwater. The quality of groundwater can differ from the quality of drinking water because water chemistry can change as a result of contact with plumbing systems or the atmosphere; because of treatment, disinfection, or blending with water from other sources; or some combination of these. Water quality in domestic wells is not regulated in California, however, to provide context for the water-quality data presented in this report, results were compared to benchmarks established for drinking-water quality. The primary comparison benchmarks were maximum contaminant levels established by the U.S. Environmental Protection Agency and the State of California (MCL-US and MCL-CA, respectively). Non-regulatory benchmarks were used for constituents without maximum contaminant levels (MCLs), including Health Based Screening Levels (HBSLs) developed by the USGS and State of California secondary maximum contaminant levels (SMCL-CA) and notification levels. Most constituents detected in samples from the Monterey–Salinas Shallow Aquifer study unit had concentrations less than their respective benchmarks.Of the 148 organic constituents analyzed in the 100 grid-well samples, 38 were detected, and all concentrations were less than the benchmarks. Volatile organic compounds were detected in 26 of the grid wells, and pesticides and pesticide degradates were detected in 28 grid wells. The special-interest constituent NDMA was detected above the HBSL in three samples, one of which also had a perchlorate concentration greater than the MCL-CA.Of the inorganic constituents, 6 were detected at concentrations above their respective MCL benchmarks in grid-well samples: arsenic (5 grid wells above the MCL of 10 micrograms per liter, μg/L), selenium (3 grid wells, MCL of 50 μg/L), uranium (4 grid wells, MCL of 30 μg/L), nitrate (16 grid wells, MCL of 10 milligrams per liter, mg/L), adjusted gross alpha particle activity (10 grid wells, MCL of 15 picocuries per liter, pCi/L), and gross beta particle activity (1 grid well, MCL of 50 pCi/L). An additional 4 inorganic constituents were detected at concentrations above their respective HBSL benchmarks in grid-well samples: boron (1 grid well above the HBSL of 6,000 μg/L), manganese (8 grid wells, HBSL of 300 μg/L), molybdenum (6 grid wells, HBSL of 40 μg/L), and strontium (6 grid wells, HBSL of 4,000 μg/L). Of the inorganic constituents, 4 were detected at concentrations above their non-health based SMCL benchmarks in grid-well samples: iron (9 grid wells above the SMCL of 300 μg/L), chloride (7 grid wells, SMCL of 500 mg/L), sulfate (14 grid wells, SMCL of 500 mg/L), and total dissolved solids (27 grid wells, SMCL of 1,000 mg/L).Of the inorganic constituents analyzed in the 70 shallow-well tap sites, 10 were detected at concentrations above the benchmarks. Of the inorganic constituents, 3 were detected at concentrations above their respective MCL benchmarks in shallow-well tap sites: arsenic (2 shallow-well tap sites above the MCL of 10 μg/L), uranium (2 shallow-well tap sites, MCL of 30 μg/L), and nitrate (24 shallow-well tap sites, MCL of 10 mg/L). An additional 3 inorganic constituents were detected above their respective HBSL benchmarks in shallow-well tap sites: manganese (4 shallow-well tap sites above the HBSL of 300 μg/L), molybdenum (4 shallow-well tap sites, HBSL of 40 μg/L), and zinc (2 shallow-well tap sites, HBSL of 2,000 μg/L). Of the inorganic constituents, 4 were detected at concentrations above their non-health based SMCL benchmarks in shallow-well tap sites: iron (6 shallow-well tap sites above the SMCL of 300 μg/L), chloride (1 shallow-well tap site, SMCL of 500 mg/L), sulfate (9 shallow-well tap sites, SMCL of 500 mg/L), and total dissolved solids (15 shallow-well tap sites, SMCL of 1,000 mg/L).

Magma reservoirs and neutral buoyancy zones on Venus - Implications for the formation and evolution of volcanic landforms

NASA Technical Reports Server (NTRS)

Head, James W.; Wilson, Lionel

1992-01-01

The production of magma reservoirs and neutral buoyancy zones (NBZs) on Venus and the implications of their development for the formation and evolution of volcanic landforms are examined. The high atmospheric pressure on Venus reduces volatile exsolution and generally serves to inhibit the formation of NBZs and shallow magma reservoirs. For a range of common terrestrial magma-volatile contents, magma ascending and erupting near or below mean planetary radius (MPR) should not stall at shallow magma reservoirs; such eruptions are characterized by relatively high total volumes and effusion rates. For the same range of volatile contents at 2 km above MPR, about half of the cases result in the direct ascent of magma to the surface and half in the production of neutral buoyancy zones. NBZs and shallow magma reservoirs begin to appear as gas content increases and are nominally shallower on Venus than on earth. For a fixed volatile content, NBZs become deeper with increasing elevation: over the range of elevations treated in this study (-1 km to +4.4 km) depths differ by a factor of 2-4. Factors that may account for the low height of volcanoes on Venus are discussed.

Ecological and evolutionary consequences of benthic community stasis in the very deep sea (>1500 m)

USGS Publications Warehouse

Buzas, Martin A.; Hayek, Lee-Ann C.; Culver, Stephen J.; Hayward, Bruce W.; Osterman, Lisa E.

2014-01-01

An enigma of deep-sea biodiversity research is that the abyss with its low productivity and densities appears to have a biodiversity similar to that of shallower depths. This conceptualization of similarity is based mainly on per-sample estimates (point diversity, within-habitat, or α-diversity). Here, we use a measure of between-sample within-community diversity (β1H) to examine benthic foraminiferal diversity between 333 stations within 49 communties from New Zealand, the South Atlantic, the Gulf of Mexico, the Norwegian Sea, and the Arctic. The communities are grouped into two depth categories: 200–1500 m and >1500 m. β1H diversity exhibits no evidence of regional differences. Instead, higher values at shallower depths are observed worldwide. At depths of >1500 m the average β1H is zero, indicating stasis or no biodiversity gradient. The difference in β1H-diversity explains why, despite species richness often being greater per sample at deeper depths, the total number of species is greater at shallower depths. The greater number of communities and higher rate of evolution resulting in shorter species durations at shallower depths is also consistent with higher β1H values.

Elimination of leukemic cells from human transplants by laser nano-thermolysis

NASA Astrophysics Data System (ADS)

Lapotko, Dmitri; Lukianova, Ekaterina; Potapnev, Michail; Aleinikova, Olga; Oraevsky, Alexander

2006-02-01

We describe novel ex vivo method for elimination of tumor cells from bone marrow and blood, Laser Activated Nano-Thermolysis for Cell Elimination Technology (LANTCET) and propose this method for purging of transplants during treatment of leukemia. Human leukemic cells derived from real patients with different diagnoses (acute lymphoblastic leukemias) were selectively damaged by LANTCET in the experiments by laser-induced micro-bubbles that emerge inside individual specifically-targeted cells around the clusters of light-absorbing gold nanoparticles. Pretreatment of the transplants with diagnosis-specific primary monoclonal antibodies and gold nano-particles allowed the formation of nanoparticle clusters inside leukemic cells only. Electron microscopy found the nanoparticulate clusters inside the cells. Total (99.9%) elimination of leukemic cells targeted with specific antibodies and nanoparticles was achieved with single 10-ns laser pulses with optical fluence of 0.2 - 1.0 J/cm2 at the wavelength of 532 nm without significant damage to normal bone marrow cells in the same transplant. All cells were studied for the damage/viability with several control methods after their irradiation by laser pulses. Presented results have proved potential applicability of developed LANTCET technology for efficient and safe purging (cleaning of residual tumor cells) of human bone marrow and blood transplants. Design of extra-corporeal system was proposed that can process the transplant for one patient for less than an hour with parallel detection and counting residual leukemic cells.

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

PubMed

Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-12-01

Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Luca; Bellini, Alberto; Stacey, Martin A.

2005-03-10

Myofibroblasts play a key role in wound closure but their origin is poorly understood. To investigate whether fibrocytes contribute to myofibroblast population, we examined the phenotype of fibrocytes and myofibroblasts present in the wounded skin of BALB/c mice. During wound healing, there was a marked increase in the number of cells expressing the myofibroblast marker {alpha}-smooth muscle actin in the granulation tissue. Between 4 and 7 days post-wounding, more than 50% of these cells also expressed the CD13 antigen. CD13{sup +}/collagen I{sup +} fibrocytes could be isolated at an early stage of the healing process from digested fragments of woundedmore » tissue by fluorescence-activated cell sorting. Like authentic fibrocytes, these cells were also CD45{sup +}/CD34{sup +}/CD14{sup -}. Between 4 and 7 days post-injury, 61.4% of the isolated fibrocytes were found to express {alpha}-smooth muscle actin gene and protein. We repeated similar experiments in female mice that had received a male whole bone marrow transplant after total body irradiation. By in situ hybridization, we identified the Y chromosome in the nuclei of the majority of fibrocytes isolated from the wounded tissue of these animals. Our data indicate that circulating fibrocytes contribute to the myofibroblast population in the wounded skin and that they originate from the bone marrow.« less

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

PubMed

Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

2012-11-01

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

Busulfan-conditioned bone marrow transplantation results in high-level allogeneic chimerism in mice made tolerant by in utero hematopoietic cell transplantation.

PubMed

Ashizuka, Shuichi; Peranteau, William H; Hayashi, Satoshi; Flake, Alan W

2006-03-01

In utero hematopoietic cell transplantation (IUHCT) is a non-ablative approach that achieves mixed allogeneic chimerism and donor-specific tolerance. However, clinical application of IUHCT has been limited by minimal engraftment. We have previously demonstrated in the murine model that low-level allogeneic chimerism achieved by IUHCT can be enhanced to near-complete donor chimerism by postnatal minimally myeloablative total body irradiation (TBI) followed by same-donor bone marrow transplantation. Because of concerns of toxicity related to even low-dose TBI in early life, we wondered if a potentially less toxic strategy utilizing a single myelosuppressive agent, Busulfan (BU), would provide similar enhancement of engraftment. In this study, mixed chimerism was created by IUHCT in a fully allogeneic strain combination. After birth, chimeric mice were conditioned with BU followed by transplantation of bone marrow cells congenic to the prenatal donor. We demonstrate that: 1) low-level chimerism after IUHCT can be converted to high-level chimerism by this protocol; 2) enhancement of chimerism is BU dose-dependent; and 3) BU reduces the proliferative potential of hematopoietic progenitor cells thus conferring a competitive advantage to the non-BU-treated postnatal donor cells. This study confirms the potential of IUHCT for facilitation of minimally toxic postnatal regimens to achieve therapeutic levels of allogeneic engraftment.

Use of concentrated bone marrow aspirate and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis

PubMed Central

Martin, John R.; Houdek, Matthew T.; Sierra, Rafael J.

2013-01-01

The aim of this paper is to describe our surgical procedure for the treatment of osteonecrosis of the femoral head using a minimally invasive technique. We have limited the use of this procedure for patients with pre-collapse osteonecrosis of the femoral head (Ficat Stage I or II). To treat osteonecrosis of the femoral head at our institution we currently use a combination of outpatient, minimally invasive iliac crest bone marrow aspirations and blood draw combined with decompressions of the femoral head. Following the decompression of the femoral head, adult mesenchymal stem cells obtained from the iliac crest and platelet rich plasma are injected into the area of osteonecrosis. Patients are then discharged from the hospital using crutches to assist with ambulation. This novel technique was utilized on 77 hips. Sixteen hips (21%) progressed to further stages of osteonecrosis, ultimately requiring total hip replacement. Significant pain relief was reported in 86% of patients (n = 60), while the rest of patients reported little or no pain relief. There were no significant complications in any patient. We found that the use of a minimally invasive decompression augmented with concentrated bone marrow and platelet rich plasma resulted in significant pain relief and halted the progression of disease in a majority of patients. PMID:23771751

Use of concentrated bone marrow aspirate and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis.

PubMed

Martin, John R; Houdek, Matthew T; Sierra, Rafael J

2013-06-01

The aim of this paper is to describe our surgical procedure for the treatment of osteonecrosis of the femoral head using a minimally invasive technique. We have limited the use of this procedure for patients with pre-collapse osteonecrosis of the femoral head (Ficat Stage I or II). To treat osteonecrosis of the femoral head at our institution we currently use a combination of outpatient, minimally invasive iliac crest bone marrow aspirations and blood draw combined with decompressions of the femoral head. Following the decompression of the femoral head, adult mesenchymal stem cells obtained from the iliac crest and platelet rich plasma are injected into the area of osteonecrosis. Patients are then discharged from the hospital using crutches to assist with ambulation. This novel technique was utilized on 77 hips. Sixteen hips (21%) progressed to further stages of osteonecrosis, ultimately requiring total hip replacement. Significant pain relief was reported in 86% of patients (n=60), while the rest of patients reported little or no pain relief. There were no significant complications in any patient. We found that the use of a minimally invasive decompression augmented with concentrated bone marrow and platelet rich plasma resulted in significant pain relief and halted the progression of disease in a majority of patients.

Cytomegalovirus infection of the BS-1 human stroma cell line: effect on murine hemopoiesis.

PubMed

Steinberg, H N; Anderson, J; Lim, B; Chatis, P A

1993-10-01

BS-1, a stromal cell line derived from human bone marrow, can support the growth of murine erythroid (BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-M) progenitor cells in a short term in vitro coculture system. Exposure of BS-1 cells to cytomegalovirus (CMV) for 3 hr prior to coculture results in a marked reduction in the stroma cell's ability to support murine hemopoiesis. CMV's effect on the BS-1 cell's hematopoietic support function is dependent on the multiplicity of infection with total suppression of BFU-E observed at a 1:1 ratio of virus to bone marrow cells. A 50% loss in the ability of BS-1 cells to support BFU-E is observed at a 0.1:1 ratio. No effect of CMV is observed with further log dilutions of virus. CMV infection of BS-1 cells affects its support of erythroid progenitor cell growth to a greater extent than its influence on the development of granulocyte-macrophage colonies. Antibody to CMV or heat inactivation of the virus reverses the inhibitory affect on BS-1 cells. The results suggest that CMV can infect a cell that constitutes one of the cellular elements of the normal bone marrow microenvironment causing a decrease in the stroma's ability to support the growth and development of normal progenitor cells.

Copper-64 Labeled Liposomes for Imaging Bone Marrow

PubMed Central

Lee, Sang-gyu; Gangangari, Kishore; Kalidindi, Teja Muralidhar; Punzalan, Blesida; Larson, Steven M.; Pillarsetty, Naga Vara Kishore

2016-01-01

Introduction Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [18F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Methods Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140 nm, and were doped with DOTA-Bn-DSPE for stable 64Cu incorporation into liposomes. Results PET imaging and biodistribution studies with 64Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18 ± 3.69 %ID/g for 90 nm liposomes and 7.01 ± 0.92 %ID/g for 140 nm liposomes at 24 h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90 nm particles is approximately 0.89 ± 0.48 %ID/g in tumor and 14.22 ± 8.07 %ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83 ± 0.49 %ID/g and 2.23 ± 1.00 %ID/g. Conclusion Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents. PMID:27694056

Hematoxylin Bodies in Pediatric Bone Marrow Aspirates and Their Utility in the Diagnosis of Systemic Lupus Erythematosus.

PubMed

Xu, Min; Chisholm, Karen M; Fan, Guang; Stevens, Anne M; Rutledge, Joe C

2017-01-01

In our recent case report, the finding of lupus erythematosus (LE) cells in a bone marrow aspirate led to the diagnosis of systemic lupus erythematosus (SLE) and appropriate treatment, although the patient was not clinically suspected to have SLE. To determine whether LE cells are present in the bone marrow aspirates of SLE patients, but overlooked in routine bone marrow morphology review, bone marrow aspirates from 30 pediatric patients (15 with SLE and 15 with other diagnoses) evaluated by rheumatologists were reviewed. LE cells were found in the bone marrow aspirates of only 1 SLE patient and none in non-SLE patients. However, hematoxylin bodies were identified in 53% (8/15) of SLE patients. Neither hematoxylin bodies nor LE cells were found in the aspirates from patients with other disorders. Three additional pediatric patients identified prospectively were found to have hematoxylin bodies in the bone marrow aspirates. Although the diagnosis was not initially suspected, 2 of the 3 patients were subsequently diagnosed with SLE. All patients with hematoxylin bodies and SLE had antinuclear antibody titers ≥1:640 with a homogeneous staining pattern. In addition, bone marrow aspirates of 9 adult patients were reviewed, and neither LE cells nor hematoxylin bodies were identified. In summary, hematoxylin bodies were present in the bone marrow aspirates of many pediatric SLE patients, while LE cells were rare. The finding of hematoxylin bodies in pediatric bone marrow aspirates is a helpful and specific diagnostic clue that may lead to the diagnosis of SLE when other clinical features are nonspecific.

Bone marrow analysis of immune cells and apoptosis in patients with systemic lupus erythematosus.

PubMed

Park, J W; Moon, S Y; Lee, J H; Park, J K; Lee, D S; Jung, K C; Song, Y W; Lee, E B

2014-09-01

To examine the immune cell profile in the bone marrow of systemic lupus erythematosus (SLE) patients and to assess its clinical relevance. Sixteen bone marrow samples from 14 SLE patients were compared with seven healthy control samples. The numbers of immune cells and apoptotic cells in the bone marrow were examined by immunohistochemistry. The association between immune cell subsets and clinical features was investigated. CD4+ T cells, macrophages and plasma cells were more common in the bone marrow of SLE patients than in healthy controls (p=0.001, p=0.004 and p<0.001, respectively). Greater numbers of CD4+ T cells and macrophages were associated with high-grade bone marrow damage. The percentage of apoptotic cells in bone marrow of SLE patients was significantly higher than that in controls (p<0.001) and was positively correlated with the number of plasmacytoid dendritic cells (p=0.013). Increased number of plasma cells along with high interleukin-6 expression was correlated with anti-double stranded DNA antibody levels and the SLE disease activity index (p=0.031 and 0.013, respectively). Bone marrow from SLE patients showed a distinct immune cell profile and increased apoptosis. This, coupled with a correlation with disease activity, suggests that the bone marrow may play a critical role in the pathogenesis of SLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

Comparison among T1-weighted magnetic resonance imaging, modified dixon method, and magnetic resonance spectroscopy in measuring bone marrow fat.

PubMed

Shen, Wei; Gong, Xiuqun; Weiss, Jessica; Jin, Ye

2013-01-01

An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods.

Comparison among T1-Weighted Magnetic Resonance Imaging, Modified Dixon Method, and Magnetic Resonance Spectroscopy in Measuring Bone Marrow Fat

PubMed Central

Shen, Wei; Gong, Xiuqun; Weiss, Jessica; Jin, Ye

2013-01-01

Introduction. An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Methods. Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Results. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. Conclusion. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods. PMID:23606951

The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls

PubMed Central

L Newton, Anna; J Hanks, Lynae; Davis, Michelle; Casazza, Krista

2013-01-01

Investigation of the physiologic relevance of bone marrow adipose tissue (BMAT) during growth may promote understanding of the bone-fat axis and confluence with metabolic factors. The objective of this pilot investigation was two-fold: (1) to evaluate the relationships among total body fat, bone mineral content (BMC) and femoral BMAT during childhood and underlying metabolic determinants and (2) to determine if the relationships differ by race. Participants included white and non-Hispanic black girls (n=59) ages 4–10 years. Femoral BMAT volume was measured by magnetic resonance imaging, BMC and body fat by dual-energy X-ray absorptiometry. Metabolic parameters were assessed in the fasted state. Total fat and BMC were positively associated with BMAT; however, simultaneous inclusion of BMC and body fat in the statistical model attenuated the association between BMC and BMAT. Differences in BMAT volume were observed, non-Hispanic black girls exhibiting marginally greater BMAT at age eight (P=0.05) and white girls exhibiting greater BMAT at age ten (P<0.001). Metabolic parameters conferred differential impact by race, such that, a positive association for BMAT and leptin (P=0.02) and adiponectin (P=0.002) in white girls while BMAT and insulin were inversely related in non-Hispanic black girls (P=0.008). Our findings revealed a positive relationship between BMAT, body fat and BMC, although body fat, respective to leptin, contributed partly to the relationship between BMAT and BMC. Despite large differences in total fat between non-Hispanic black and white, the relationship between BMAT and BMC was similar to white girls. However, this relationship appeared to be impacted through different mechanisms according to race. PMID:23951544

The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls.

PubMed

L Newton, Anna; J Hanks, Lynae; Davis, Michelle; Casazza, Krista

2013-01-01

Investigation of the physiologic relevance of bone marrow adipose tissue (BMAT) during growth may promote understanding of the bone-fat axis and confluence with metabolic factors. The objective of this pilot investigation was two-fold: (1) to evaluate the relationships among total body fat, bone mineral content (BMC) and femoral BMAT during childhood and underlying metabolic determinants and (2) to determine if the relationships differ by race. Participants included white and non-Hispanic black girls (n=59) ages 4-10 years. Femoral BMAT volume was measured by magnetic resonance imaging, BMC and body fat by dual-energy X-ray absorptiometry. Metabolic parameters were assessed in the fasted state. Total fat and BMC were positively associated with BMAT; however, simultaneous inclusion of BMC and body fat in the statistical model attenuated the association between BMC and BMAT. Differences in BMAT volume were observed, non-Hispanic black girls exhibiting marginally greater BMAT at age eight (P=0.05) and white girls exhibiting greater BMAT at age ten (P<0.001). Metabolic parameters conferred differential impact by race, such that, a positive association for BMAT and leptin (P=0.02) and adiponectin (P=0.002) in white girls while BMAT and insulin were inversely related in non-Hispanic black girls (P=0.008). Our findings revealed a positive relationship between BMAT, body fat and BMC, although body fat, respective to leptin, contributed partly to the relationship between BMAT and BMC. Despite large differences in total fat between non-Hispanic black and white, the relationship between BMAT and BMC was similar to white girls. However, this relationship appeared to be impacted through different mechanisms according to race.

Mycobacterium tuberculosis Contaminant Risk on Bone Marrow Aspiration Material from Iliac Bone Patients with Active Tuberculous Spondylitis.

PubMed

Rahyussalim, Ahmad Jabir; Kurniawati, Tri; Rukmana, Andriansjah

2016-01-01

There was a concern on Mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. This research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. As many as nine patients with tuberculous spondylitis were used as samples. During the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria culture, and PCR (polymerase chain reaction) tests for Mycobacterium tuberculosis at the Clinical Microbiology Laboratory of Faculty of Medicine Universitas Indonesia. This research showed that there was a relationship between diagnostic confirmation of tuberculous spondylitis based on the PCR test and bacterial culture on the solid vertebral lesion material with the PCR test and bacterial culture from the bone marrow aspirates. If the diagnostic confirmation concluded positive results, then there was a higher probability that there would be a positive result for the bone marrow aspirates, so that it was not recommended to use autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis unless the PCR and culture examination of the bone marrow showed a negative result.

An Association between BK Virus Replication in Bone Marrow and Cytopenia in Kidney-Transplant Recipients

PubMed Central

Pambrun, Emilie; Mengelle, Catherine; Fillola, Geneviève; Laharrague, Patrick; Esposito, Laure; Cardeau-Desangles, Isabelle; Del Bello, Arnaud; Izopet, Jacques; Rostaing, Lionel; Kamar, Nassim

2014-01-01

The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often occur in kidney-transplant patients. However, it is unknown if BKV can replicate within bone marrow. The aim of this study was to search for BKV replication within the bone marrow of kidney-transplant patients presenting with a hematological disorder. Seventy-two kidney-transplant patients underwent bone-marrow aspiration for cytopenia. At least one virus was detected in the bone marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV replication within the bone marrow had no detectable BKV replication in the blood. Neutropenia was observed in all patients with BKV replication in the bone marrow, and blockade of granulocyte maturation was observed. Hematological disorders disappeared in all patients after doses of immunosuppressants were reduced. In conclusion, an association between BKV replication in bone marrow and hematological disorders, especially neutropenia, was observed. Further studies are needed to confirm these findings. PMID:24868448

Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

PubMed

Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

2017-03-07

Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

Question of bone marrow stromal fibroblast traffic

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

L-Leucyl-L-Leucine Methyl Ester Treatment of Canine Marrow and Peripheral Blood Cells: Inhibition of Proliferative Responses with Maintenance of the Capacity for Autologous Marrow Engraftment

DTIC Science & Technology

1988-11-01

Copyright 0 198 by The Winiams & Wilkins Co. Printed in U.S.A. L-LEUCYL-L-LEUCINE METHYL ESTER TREATMENT OF CANINE MARROW AND PERIPHERAL BLOOD CELLS...Reearch CeThs eatetle, Washington 9%104 tInaiyuba on o canine UMrrowt and peripher hi Recently, Thiele and Lipsky have described adipeptide nionon clear...that marrow iincubation with Leu-Leu. Leu-Leu-OMe is a feasible method to deplete canine marrows of aloreactive and cytotoxic T cells prior to OMe

Entrainment of viruses from septic tank leach fields through a shallow, sandy soil aquifer.

PubMed

Vaughn, J M; Landry, E F; Thomas, M Z

1983-05-01

A study was conducted which focused on movement of naturally occurring human enteroviruses from a subsurface wastewater disposal system through a shallow aquifer. The potential for significant entrainment of virus particles was evidenced by their recovery at down-gradient distances of 67.05 m and from aquifer depths of 18 m. A significant negative correlation was observed between virus occurrence and the distance from the "septage" (leaching pool) source. Virus occurrence could not be statistically correlated with either total or fecal coliforms, indicating the limitations of current microbial water quality indicators for predicting the virological quality of groundwater.

Graft-versus-host disease

MedlinePlus

GVHD; Bone marrow transplant - graft-versus-host disease; Stem cell transplant - graft-versus-host disease; Allogeneic transplant - ... GVHD may occur after a bone marrow, or stem cell, transplant in which someone receives bone marrow ...

Bone Marrow Failure Secondary to Cytokinesis Failure

DTIC Science & Technology

2015-12-01

SUPPLEMENTARY NOTES 14. ABSTRACT Fanconi anemia (FA) is a human genetic disease characterized by a progressive bone marrow failure and heightened...Fanconi anemia (FA) is the most commonly inherited bone marrow failure syndrome. FA patients develop bone marrow failure during the first decade of...experiments proposed in specific aims 1- 3 (Tasks 1-3). Task 1: To determine whether HSCs from Fanconi anemia mouse models have increased cytokinesis

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

NASA Astrophysics Data System (ADS)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient radiopharmaceutical for the treatment of bone metastases than 153Sm and 89Sr, if the diffusion of 219Rn to the bone marrow is insignificant.

Is fatty acid composition of human bone marrow significant to bone health?

PubMed

Pino, Ana María; Rodríguez, J Pablo

2017-12-16

The bone marrow adipose tissue (BMAT) is a conserved component of the marrow microenvironment, providing storage and release of energy and stabilizing the marrow extent. Also, it is recognized both the amount and quality of BMAT are relevant to preserve the functional relationships between BMAT, bone, and blood cell production. In this article we ponder the information supporting the tenet that the quality of BMAT is relevant to bone health. In the human adult the distribution of BMAT is heterogeneous over the entire skeleton, and both BMAT accumulation and bone loss come about with aging in healthy populations. But some pathological conditions which increase BMAT formation lead to bone impairment and fragility. Analysis in vivo of the relative content of saturated and unsaturated fatty acids (FA) in BMAT indicates site-related bone marrow fat composition and an association between increased unsaturation index (UI) and bone health. With aging some impairment ensues in the regulation of bone marrow cells and systemic signals leading to local chronic inflammation. Most of the bone loss diseases which evolve altered BMAT composition have as common factors aging and/or chronic inflammation. Both saturated and unsaturated FAs originate lipid species which are active mediators in the inflammation process. Increased free saturated FAs may lead to lipotoxicity of bone marrow cells. The pro-inflammatory, anti-inflammatory or resolving actions of compounds derived from long chain poly unsaturated FAs (PUFA) on bone cells is varied, and depending on the metabolism of the parent n:3 or n:6 PUFAs series. Taking together the evidence substantiate that marrow adipocyte function is fundamental for an efficient link between systemic and marrow fatty acids to accomplish specific energy or regulatory needs of skeletal and marrow cells. Further, they reveal marrow requirements of PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.

Total energy and potential enstrophy conserving schemes for the shallow water equations using Hamiltonian methods $-$ Part 1: Derivation and properties

DOE PAGES

Eldred, Christopher; Randall, David

2017-02-17

The shallow water equations provide a useful analogue of the fully compressible Euler equations since they have similar characteristics: conservation laws, inertia-gravity and Rossby waves, and a (quasi-) balanced state. In order to obtain realistic simulation results, it is desirable that numerical models have discrete analogues of these properties. Two prototypical examples of such schemes are the 1981 Arakawa and Lamb (AL81) C-grid total energy and potential enstrophy conserving scheme, and the 2007 Salmon (S07) Z-grid total energy and potential enstrophy conserving scheme. Unfortunately, the AL81 scheme is restricted to logically square, orthogonal grids, and the S07 scheme is restrictedmore » to uniform square grids. The current work extends the AL81 scheme to arbitrary non-orthogonal polygonal grids and the S07 scheme to arbitrary orthogonal spherical polygonal grids in a manner that allows for both total energy and potential enstrophy conservation, by combining Hamiltonian methods (work done by Salmon, Gassmann, Dubos, and others) and discrete exterior calculus (Thuburn, Cotter, Dubos, Ringler, Skamarock, Klemp, and others). Lastly, detailed results of the schemes applied to standard test cases are deferred to part 2 of this series of papers.« less

Spatial variability of the shallow groundwater level and its chemistry characteristics in the low plain around the Bohai Sea, North China.

PubMed

Zhou, Zaiming; Zhang, Guanghui; Yan, Mingjiang; Wang, Jinzhe

2012-06-01

To characterize the spatial distribution of groundwater level (GWL) and its chemistry characteristics in the low plain around the Bohai Sea, shallow groundwater depth of 130 wells were determined. Water soluble ions composition, total dissolved solid (TDS), electric conductivity (EC), total hardness (TH), total alkalinity (TA), and total salt content (TS) of 128 representative groundwater samples were also measured. Classical statistics, geostatistical method combined with GIS technique were then used to analyze the spatial variability and distribution of GWL and groundwater chemical properties. Results show that GWL, TDS, EC, TH, TA, and TS all presented a lognormal distribution and could be fitted by different semivariogram models (spherical, exponential, and Gaussian). Spatial structure of GWL, TDS, EC, TH, TA, and TS changed obviously. GWL decreased from west inland plain to the east coastal plain, however, TDS, EC, and TS increased from west to east, TH and TA were higher in the middle and coastal plain area. Groundwater chemical type in the coastal plain was SO (4) (2-) ·Cl(-)-Na(+) while chemical types in the inland plain were SO (4) (2-) ·Cl(-)-Ca(2+)·Mg(2+) and HCO (3) (-) -Ca(2+)·Mg(2+).

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Occurrence, spatiotemporal distribution, and ecological risks of steroids in a large shallow Chinese lake, Lake Taihu.

PubMed

Zhou, Li-Jun; Zhang, Bei-Bei; Zhao, Yong-Gang; Wu, Qinglong L

2016-07-01

Steroids have been frequently detected in surface waters, and might pose adverse effects on aquatic organisms. However, little information is available regarding the occurrence and spatiotemporal distribution of steroids in lake environments. In addition to pollution sources, the occurrence and spatiotemporal distribution of steroids in lake environments might be related to lake types (shallow or deep), lake hydrodynamics, and sorption-desorption processes in the water-sediment systems. In this study, the occurrence, spatiotemporal distribution, and ecological risks of 36 steroids in a large shallow lake were evaluated by investigating surface water and sediment samples at 32 sites in Lake Taihu over two seasons. Twelve and 15 analytes were detected in aqueous and sedimentary phases, respectively, with total concentrations ranging from 0.86 to 116ng/L (water) and from 0.82 to 16.2ng/g (sediment, dry weight). Temporal variations of steroid concentrations in the water and sediments were statistically significant, with higher concentrations in winter. High concentrations of steroids were found in the seriously polluted bays rather than in the pelagic zone of the lake. Strong lake currents might mix pelagic waters, resulting in similar concentrations of steroids in the pelagic zone. Mass balance analysis showed that sediments in shallow lakes are in general an important sink for steroids. Steroids in the surface water and sediments of Lake Taihu might pose potential risks to aquatic organisms. Overall, our study indicated that the concentrations and spatiotemporal distribution of steroids in the large shallow lake are influenced simultaneously by pollution sources and lake hydrodynamics. Steroids in the large shallow Lake Taihu showed clear temporal and spatial variations and lake sediments may be a potential sink of steroids. Copyright © 2016 Elsevier B.V. All rights reserved.

Evidence for the Activation of Shallow Preferential Flow Paths in a Tropical Panama Watershed Using Germanium and Silicon

NASA Astrophysics Data System (ADS)

Gardner, Christopher B.; Litt, Guy F.; Lyons, W. Berry; Ogden, Fred L.

2017-10-01

In humid tropical watersheds, the hydrologic flow paths taken by rain event waters and how they interact with groundwater and soil matrix water to form streamflow are poorly understood. Preferential flow paths (PFPs) confound storm infiltration processes, especially in the humid tropics where PFPs are common. This work applies germanium (Ge) and silicon (Si) as natural flow path tracers in conjunction with water stable isotopes and electrical conductivity to examine the rapid delivery of shallow soil water, the activation of PFPs, and event water partitioning in an experimental catchment in central Panama. We employed a three-component mixing model for hydrograph separation using the following end-member waters: (i) base flow (high [Si], low [Ge], and low Ge/Si ratio), (ii) dilute canopy throughfall (low [Si] and low [Ge]), and (iii) shallow (<15 cm) soil matrix water (low [Si], high [Ge], and high Ge/Si ratio). These three end-members bounded all observed Ge/Si streamflow ratios. During small rain events (<˜24 mm), base flow and dilute canopy throughfall components dominated stormflow. During larger precipitation events (>˜35 mm), we detected the third shallow soil water component with an elevated [Ge] and Ge/Si ratio. This component reached its maximum during the hydrograph's receding limb coincident with the maximum event fraction, and increased proportionally to the total storm rainfall exceeding ˜35 mm. Only shallow (<15 cm) soil matrix water exhibited elevated Ge concentrations and high Ge/Si ratios. This third component represents rapidly delivered soil matrix water combined with shallow lateral PFP activation through which event waters interact with soil minerals.

Consistency of temporal and habitat-related differences among assemblages of fish in coastal lagoons

NASA Astrophysics Data System (ADS)

Gray, Charles A.; Rotherham, Douglas; Johnson, Daniel D.

2011-12-01

The consistency of habitat-related differences in coastal lagoon fish assemblages was assessed across different spatial and temporal scales. Multimesh gillnets were used to sample assemblages of fish on a monthly basis for 1-year in three habitats (shallow seagrass, shallow bare and deep substrata) at two locations (>1 km apart), in each of two coastal lagoons (approximately 500 km apart), in southeastern Australia. A total of 48 species was sampled with 34 species occurring in both lagoons and in all three habitats; species caught in only one lagoon or habitat occurred in low numbers. Ten species dominated assemblages and accounted for more than 83% of all individuals sampled. In both lagoons, assemblages in the deep habitat consistently differed to those in the shallow strata (regardless of habitat). Several species were caught more frequently or in larger numbers in the deep habitat. Assemblages in the two shallow habitats did not differ consistently and were dominated by the same species and sizes of fish, possibly due to habitat heterogeneity and the scale and method of sampling. Within each lagoon, very few between location differences in assemblages within each habitat were observed. Consistent differences in assemblages were detected between lagoons for the shallow bare and deep habitats, indicating there were some intrinsic differences in ichthyofauna between lagoons. Assemblages in spring differed to those in summer, which differed to those in winter for the shallow bare habitat in both lagoons, and the deep habitat in only one lagoon. Fish-habitat relationships are complex and differences in the fish fauna between habitats were often temporally inconsistent. This study highlights the need for greater testing of habitat relationships in space and time to assess the generality of observations and to identify the processes responsible for structuring assemblages.

Immune response

MedlinePlus Videos and Cool Tools

... These cells develop into two groups in the bone marrow. From the bone marrow, one group of lymphocytes migrates to a ... or B cells, mature and develop within the bone marrow itself. In that process, they achieve the ...

[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.

Isolated juvenile xanthogranuloma in the bone marrow: report of a case and review of the literature.

PubMed

Kesserwan, Chimen; Boué, Daniel R; Kahwash, Samir B

2007-01-01

We report a case of juvenile xanthogranuloma limited to involvement of the bone marrow in a 6-week-old male infant. Evaluation of the bone marrow was a part of the workup for peripheral blood cytopenia. Examination showed hypercellular marrow with paratrabecular clusters of lipidized histiocytes positive for CD68, CD4, and factor XIII(a) and negative for S100 and CD1a. Clinical and radiological workup showed no associated skin lesions or osseous or visceral involvement. The patient was started on chemotherapy with clinical improvement and gradual decreased bone marrow involvement. The child is alive and well at 16 months of age. This case represents, to the best of our knowledge, the 1st documented case of juvenile xanthogranuloma with isolated bone marrow involvement sparing skin and viscera.

Survival and endogenous colony formation in irradiated mice grafted with normal or infectious mononucleosis bone marrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louwagie, A. C.; Verwilghen, R. L.

1973-07-01

Mice were exposed to 850 or 975 rad of whole-body radiation; three hr later mice were given normal human bone marrow, infectious mononucleosis bone marrow, or cells from malignant blood diseases. The surviving mice were killed at day 9 and the spleen nodules were counted. Some mice were also given antihuman antilymphocytic serum (ALS). In mice exposed to 975 rad, the highest survival was observed in mice grafted with infectious mononucleosis bone marrow, while none of the animals grafted with cells from malignant blood diseases survived 9 days. In mice exposed to 850 rad, grafting of normal or infectious mononucleosismore » bone marrow markedly decreased the survival. Endogenous spleen colonies were induced in all animals grafted with normal or infectious mononucleosis bone marrow. (HLW)« less

Shallow peatland ecohydrology - the control of peat depth on moss productivity

NASA Astrophysics Data System (ADS)

Dixon, Simon; Kettridge, Nicholas; Moore, Paul; Devito, Kevin; Tilak, Amey; Petrone, Rich; Mendoza, Carl; Waddington, Mike

2017-04-01

Northern peatlands represent an important sink in the global carbon cycle. Shallow peatlands and marginal connective wetlands can be essential components of many northern peatland landscape mosaics, playing a vital role in landscape connectivity and wider landscape hydrology. However the ecohydrological function of these shallow, marginal systems has been largely overlooked, with peatland hydrology research focused on relatively deep bog systems. In order to predict landscape scale wetland function and its vulnerability to climate change we need to understand how these shallow connective systems function. The balance between moss productivity and water loss provide a key component of these systems, as water use efficiency controls the rate of moss growth and thus controls the amount of atmospheric carbon sequestered in peat. Understanding how productivity of shallow peatland systems responds to changes in evaporative stress will aid predictions of peatland landscape hydrological function in a changing climate. To determine the factors influencing peat productivity, water balance simulations using Hydrus 1-D were conducted over annual growing seasons for different soil profile depths, compositions and antecedent moisture conditions. Our results demonstrate a bimodal distribution of peatland responses; either primarily conserving water by limiting evapotranspiration or, maximizing productivity. For sustained periods of evaporative stress, shallow marginal systems are least able to buffer periods of evaporative stress due to limited labile water storage, and will limit evaporation, conserve water and be less productive. Conversely, where present, both deep water storage and a shallow initial water table prolong the onset of high vegetative stress, thus maximizing moss productivity. However, a total depth of 0.8 m is identified as the threshold above which increasing peat depth has no further effect on changing vegetative stress response and thus landscape function. These results are important as moss productivity, along with rate of organic matter decay are the two principle factors controlling the build-up of peat, and therefore sequestration of carbon. With a predicted increase in the frequency and size of rain events in northern latitudes our results indicate the productivity of shallow wetland systems may increase, but greater moisture availability will increase the likelihood they remain as wetlands in a changing climate.

Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity

PubMed Central

Zhang, Michael Y.; Keel, Siobán B.; Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Watts, Amanda C.; Pritchard, Colin C.; Salipante, Stephen J.; Jeng, Michael R.; Hofmann, Inga; Williams, David A.; Fleming, Mark D.; Abkowitz, Janis L.; King, Mary-Claire; Shimamura, Akiko

2015-01-01

Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes. PMID:25239263

Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women.

PubMed

Pino, Ana María; Ríos, Susana; Astudillo, Pablo; Fernández, Mireya; Figueroa, Paula; Seitz, Germán; Rodríguez, J Pablo

2010-03-01

Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor kappaB ligand (s-RANKL), tumor necrosis factor alpha, and interleukin 6 (IL-6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above-mentioned cytokines and also the level of the soluble receptors for both IL-6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual-energy X-ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines' concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic BMSF differentiated by decreased leptin bioavailability, suggesting that insufficient leptin action may distinguish the osteoporotic bone marrow. Copyright 2010 American Society for Bone and Mineral Research.

Granulocyte-mobilized bone marrow.

PubMed

Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

2012-11-01

In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

Precipitation patterns and moisture fluxes in a sandy, tropical environment with a shallow water table

NASA Astrophysics Data System (ADS)

Minihane, M. R.; Freyberg, D. L.

2011-08-01

Identifying the dominant mechanisms controlling recharge in shallow sandy soils in tropical climates has received relatively little attention. Given the expansion of coastal fill using marine sands and the growth of coastal populations throughout the tropics, there is a need to better understand the nature of water balances in these settings. We use time series of field observations at a coastal landfill in Singapore coupled with numerical modeling using the Richards' equation to examine the impact of precipitation patterns on soil moisture dynamics, including percolation past the root zone and recharge, in such an environment. A threshold in total precipitation event depth, much more so than peak precipitation intensity, is the strongest event control on recharge. However, shallow antecedent moisture, and therefore the timing between events along with the seasonal depth to water table, also play significant roles in determining recharge amounts. For example, at our field site, precipitation events of less than 3 mm per event yield little to no direct recharge, but for larger events, moisture content changes below the root zone are linearly correlated to the product of the average antecedent moisture content and the total event precipitation. Therefore, water resources planners need to consider identifying threshold precipitation volumes, along with the multiple time scales that capture variability in event antecedent conditions and storm frequency in assessing the role of recharge in coastal water balances in tropical settings.

Seasonal and diel habitat selection by bluegills in a shallow natural lake

USGS Publications Warehouse

Paukert, C.P.; Willis, D.W.

2002-01-01

Habitat use by bluegill Lepomis macrochirus may be dictated by the avoidance of predators and the availability of prey. Previous work suggests that bluegills large enough to avoid predators will select habitats based on foraging profitability. However, these studies focused on smaller fish (200 mm total length [TL]) bluegills in a shallow (mean depth = 1.2 m), 332-ha, natural lake (Pelican Lake, Nebraska) with both emergent and submergent vegetation distributed throughout. A total of 78 bluegills (200-273 mm TL) were implanted with radio transmitters and relocated daily for 6 d per month (April-September); up to 20 of the tagged fish were relocated every 2 h for a 24-h period once each month. Regardless of diel period, bluegills used open-water, emergent vegetation, submergent vegetation, and mixed emergent - submergent vegetation habitat types in similar proportions. During April, June, and July, male bluegills positively selected emergent vegetation, whereas female bluegills showed no vegetation selection preference during any month. Throughout the study period, bluegills never avoided open-water habitats, suggesting that larger individuals may continue to use open-water habitats in proportion to their availability. In addition, emergent vegetation appeared to be important, particularly for male bluegills. Although the mechanism for the positive selection of emergent vegetation by males was unclear, the protection or enhancement of such habitats may facilitate the preservation of quality bluegill populations in shallow lakes.

Getting to the Heart of Being the Match: A Qualitative Analysis of Bone Marrow Donor Recruitment and Retention among College Students

ERIC Educational Resources Information Center

Kaster, Elizabeth C.; Rogers, Charles R.; Jeon, Kwon Chan; Rosen, Brittany

2014-01-01

Introduction: For those with certain blood or bone cancers, bone marrow donation can mean the difference between life and death. The National Marrow Donor Program® (NMDP) operates the largest bone marrow registry of potential donors; however, at times when potential matches are identified, many donors opt not to donate. The purpose of this study…

The bone marrow is not only a primary lymphoid organ: The critical role for T lymphocyte migration and housing of long-term memory plasma cells.

PubMed

Pabst, Reinhard

2018-05-22

In immunology and anatomy textbooks the bone marrow is described as a typical "primary lymphoid organ" producing lymphoid cells independent of antigens. The hematopoietic bone marrow is largely age-dependent organ with great anatomical and functional differences among various species. There are estimates that about 12% of all lymphoid cells in the human body are found in the bone marrow at any given time (2% in the peripheral blood). Enormous numbers of T lymphocytes migrate to the bone marrow and partly return later to the blood. Many of these lymphocytes are memory CD4 + and CD8 + T cells. A few days after immunization a wave of plasma cells and their precursors migrate to the bone marrow where they lose their migratory response to CXCL-12 and CXCL9. There is a relative enrichment of CD19 + B cells in the bone marrow outnumbering those in the blood and secondary lymphoid organs. This is not due to local production. The proliferation and migration kinetics of these lymphoid cells in the bone marrow have to be studied in more detail as this is of major clinical relevance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Can bone marrow differentiate into renal cells?

PubMed

Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract

PubMed Central

THAM, CHING S.; CHAKRAVARTHI, SRIKUMAR; HALEAGRAHARA, NAGARAJA; DE ALWIS, RANJIT

2013-01-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis. PMID:23403524

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract.

PubMed

Tham, Ching S; Chakravarthi, Srikumar; Haleagrahara, Nagaraja; DE Alwis, Ranjit

2013-02-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis.

Automated classification of bone marrow cells in microscopic images for diagnosis of leukemia: a comparison of two classification schemes with respect to the segmentation quality

NASA Astrophysics Data System (ADS)

Krappe, Sebastian; Benz, Michaela; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

2015-03-01

The morphological analysis of bone marrow smears is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually with the use of bright field microscope. This is a time consuming, partly subjective and tedious process. Furthermore, repeated examinations of a slide yield intra- and inter-observer variances. For this reason an automation of morphological bone marrow analysis is pursued. This analysis comprises several steps: image acquisition and smear detection, cell localization and segmentation, feature extraction and cell classification. The automated classification of bone marrow cells is depending on the automated cell segmentation and the choice of adequate features extracted from different parts of the cell. In this work we focus on the evaluation of support vector machines (SVMs) and random forests (RFs) for the differentiation of bone marrow cells in 16 different classes, including immature and abnormal cell classes. Data sets of different segmentation quality are used to test the two approaches. Automated solutions for the morphological analysis for bone marrow smears could use such a classifier to pre-classify bone marrow cells and thereby shortening the examination duration.

Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krieg, A.M.; Gourley, M.F.; Steinberg, A.D.

1991-05-01

Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymicmore » epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells.« less

Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Park, Jae Yong; Kim, Sang Gyun; Kim, Joo Sung; Jung, Hyun Chae

2016-01-01

The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved. To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up. Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed. Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%). Bone marrow involvement was rare in patients with only superficial gastric MALT lymphoma without extragastric invasion. Further studies are warranted to identify the risk factors of bone marrow involvement in gastric MALT lymphoma. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

PubMed

Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

2015-11-01

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

Shallow ground-water quality beneath a major urban center: Denver, Colorado, USA

USGS Publications Warehouse

Bruce, B.W.; McMahon, P.B.

1996-01-01

A survey of the chemical quality of ground water in the unconsolidated alluvial aquifer beneath a major urban center (Denver, Colorado, USA) was performed in 1993 with the objective of characterizing the quality of shallow ground-water in the urban area and relating water quality to land use. Thirty randomly selected alluvial wells were each sampled once for a broad range of dissolved constituents. The urban land use at each well site was sub- classified into one of three land-use settings: residential, commercial, and industrial. Shallow ground-water quality was highly variable in the urban area and the variability could be related to these land-use setting classifications. Sulfate (SO4) was the predominant anion in most samples from the residential and commercial land-use settings, whereas bicarbonate (HCO3) was the predominant anion in samples from the industrial land-use setting, indicating a possible shift in redox conditions associated with land use. Only three of 30 samples had nitrate concentrations that exceeded the US national drinking-water standard of 10 mg l-1 as nitrogen, indicating that nitrate contamination of shallow ground water may not be a serious problem in this urban area. However, the highest median nitrate concentration (4.2 mg l-1) was in samples from the residential setting, where fertilizer application is assumed to be most intense. Twenty-seven of 30 samples had detectable pesticides and nine of 82 analyzed pesticide compounds were detected at low concentrations, indicating that pesticides are widely distributed in shallow ground water in this urban area. Although the highest median total pesticide concentration (0.17 ??g l-1) was in the commercial setting, the herbicides prometon and atrazine were found in each land-use setting. Similarly, 25 of 29 samples analyzed had detectable volatile organic compounds (VOCs) indicating these compounds are also widely distributed in this urban area. The total VOC concentrations in sampled wells ranged from nondetectable to 23 442 ??g l-1. Widespread detections and occasionally high concentrations point to VOCs as the major anthropogenic ground-water impact in this urban environment. Generally, the highest VOC concentrations occurred in samples from the industrial setting. The most frequently detected VOC was the gasoline additive methyl tertbutyl ether (MTBE, in 23 of 29 wells). Results from this study indicate that the quality of shallow ground water in major urban areas can be related to land-use settings. Moreover, some VOCs and pesticides may be widely distributed at low concentrations in shallow ground water throughout major urban areas. As a result, the differentiation between point and non-point sources for these compounds in urban areas may be difficult.

An investigation of shallow ground-water quality near East Fork Poplar Creek, Oak Ridge, Tennessee

USGS Publications Warehouse

Carmichael, J.K.

1989-01-01

Alluvial soils of the flood plain of East Fork Poplar Creek in Oak Ridge, Tennessee, are contaminated with mercury and other metals, organic compounds, and radio-nuclides originating from the Y-12 Plant, a nuclear-processing facility located within the U.S. Department of Energy 's Oak Ridge Reservation. Observation wells were installed in the shallow aquifer of the flood plain, and water quality samples were collected to determine if contaminants are present in the shallow groundwater. Groundwater in the shallow aquifer occurs under water-table conditions. Recharge is primarily from precipitation and discharge is to East Fork Poplar Creek. Groundwater levels fluctuate seasonally in response to variations in recharge and evapotranspiration. During extremely dry periods, the water table drops below the base of the shallow aquifer in some flood-plain areas. Contaminants found in water samples from several of the wells in concentrations which equaled or exceeded drinking-water standards established by the U.S. Environmental Protection Agency are antimony, chromium, lead, mercury, selenium, phenols, and strontium-90. Total and dissolved uranium concentrations exceeded the analytical detection limit in nearly 70% of the wells in the flood plain. The results of water quality determinations demonstrate that elevated concentrations of most trace metals (and possibly organic compounds and radionuclides) were caused by contaminated sediments in the samples. The presence of contaminated sediment in samples is suspected to be the result of borehole contamination during well installation. (USGS)

Bone-marrow transplant - series (image)

MedlinePlus

Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia or ... Bone-marrow transplants prolong the life of patients who might otherwise die. As with all major organ transplants, however, ...

Neutrophil Kinetics in Acute Infection*

PubMed Central

Marsh, J. C.; Boggs, D. R.; Cartwright, G. E.; Wintrobe, M. M.

1967-01-01

Neutrophil kinetics of acute experimental infection were studied with diisopropylfluorophosphate-32P labeling in 31 dogs inoculated intrabronchially with pneumococci. In vitro neutrophil labeling indicated a rapid transit time through the blood in early infections, with an elevated marginal granulocyte pool sometimes preceding an elevation of the circulating granulocyte pool. 13 hr after infection, the circulating and total blood granulocyte pools were increased but the rate of neutrophil transit through the blood was normal. During the recovery from infection there was a marked prolongation of neutrophil blood transit time, suggesting virtually complete cessation of bone marrow release of neutrophils into the blood. Labeling of neutrophils in vivo indicated an increased rate of emptying of the bone marrow storage pool proportional to the severity of infection as measured by the fever index. The change in the blood ratio of nonsegmented to segmented neutrophils was a much more accurate index of the severity of infection than the blood granulocyte concentration, correlating significantly with the fever index. PMID:6073999

Hairy-cell leukemia: a rare blood disorder in Asia.

PubMed

Josephine, F P; Nissapatorn, V

2006-01-01

We report a 68-year-old Indian man who was referred to the Hematology Unit for investigation for thrombocytopenia, an incidental finding during a pre-operative screening for prostatectomy. Physical examination was unremarkable. There was no splenomegaly, hepatomegaly or lymphadenopathy. Complete blood counts showed normal hemoglobin and total white cell count with moderate thrombocytopenia. Hairy-cell leukemia was diagnosed based on peripheral blood film, bone-marrow aspirate and trephine biopsy findings, supported by immunophenotyping results by flow cytometry. The purpose of this report is to create awareness of this uncommon presentation and to emphasize that a single-lineage cytopenia or absence of splenomegaly does not exclude the diagnosis of hairy-cell leukemia. Careful attention to morphological detail is important for early diagnosis, especially when low percentages of "hairy" cells are present in the peripheral blood and bone marrow. Early diagnosis is important to ensure that patients obtain maximum benefit from the newer therapeutic agents that have greatly improved the prognosis in this rare disorder.

[Ocular graft-versus-host disease: An often misdiagnosed etiology of dry eye syndrome].

PubMed

Moyal, L; Adam, R; Akesbi, J; Rodallec, F T; Nordmann, J-P

2017-02-01

To report a case of severe ocular graft-versus-host disease (GVHD) after cataract surgery. Observational case report. We describe the case of a 59-year-old man with postoperative corneal ulcer on his only functional eye. His past history reported allogenic bone marrow transplant. His visual acuity (VA) was limited to hand motions. Slit lamp examination revealed diffuse conjunctival hyperemia, severe blepharitis, Meibomian dysfunction, total corneal opacification with epithelial and stromal keratitis and neovascular invasion. Because of the severe dry eye symptoms and history of allogenic hematological stem cell transplantation, ocular GVHD was diagnosed. Functional and anatomical improvement occurred rapidly with topical cyclosporine 2%, with improved VA after treatment. With any severe dry eye syndrome in the context of allogenic bone marrow transplant, ocular GVHD must be considered. For planned ocular surgery, we recommend adding cyclosporine 0.1% treatment before and after surgery to prevent severe ocular GVHD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Three further triterpenoid saponins from Gleditsia caspica fruits and protective effect of the total saponin fraction on cyclophosphamide-induced genotoxicity in mice.

PubMed

Melek, Farouk R; Aly, Fawzia A; Kassem, Iman A A; Abo-Zeid, Mona A M; Farghaly, Ayman A; Hassan, Zeinab M

2015-01-01

Three triterpenoidal saponins were isolated from the saponin fraction derived from a Gleditsia caspica Desf. methanolic fruit extract. The isolated saponins were identified as gleditsiosides B, C, and Q based on spectral data. The saponin-containing fraction was evaluated in vivo for genotoxic and antigenotoxic activities. The fraction caused no DNA damage in Swiss albino male mice treated with a dose of 45 mg/kg body weight for 24 h, although it significantly inhibited the number of chromosomal aberrations induced by cyclophosphamide (CP) in bone marrow and germ cells when applied before or after CP administration. The inhibitory indices in chromosomal aberrations were 59% and 41% for bone marrow and 48% and 43% for germ cells, respectively. In addition, the saponin fraction was found to reduce the viability of the human tumor cell line MCF-7 in a dose-dependent manner with an extrapolated IC50 value in the range of 220 μg/mL.

Pilot study of erlotinib in patients with acute myeloid leukemia.

PubMed

Sayar, Hamid; Czader, Magdalena; Amin, Chirag; Cangany, Mary; Konig, Heiko; Cripe, Larry D

2015-02-01

We conducted a pilot study to investigate clinical efficacy of tyrosine kinase inhibitor erlotinib in the treatment of acute myeloid leukemia (AML). A total of 11 patients with de novo AML were treated, including 2 with relapsed and/or refractory disease and 9 older patients with previously untreated AML. Patients with high baseline leukocyte count were excluded. Erlotinib was given orally at 150 mg per day continuously in 28-day cycles. The treatment was tolerated well, and no toxicities were observed. An initial reduction in circulating blasts, followed by disease progression, was observed in 2 patients. Nine other patients did not demonstrate any response in blood or bone marrow. Baseline and post-cycle 1 flow-cytometry were performed on bone marrow blasts to investigate signs of differentiation. No immunophenotypic changes suggestive of differentiation were observed. This pilot study did not demonstrate response to standard doses of erlotinib in patients with AML. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nucleomedical studies on the reticuloendothelial system in bone marrow. 5. Reticuloendothelial uptake of intravenous hemolysates: a simulation of the intravascular hemolytic sequelae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okuyama, S.; Ito, Y.; Sato, T.

1972-11-01

In exploration of prospects and possible limitations of /sup 113m/ Inchondroitin sulfate colloid (/sup 113m/In-ChS) as an improved bone marrow seeker developed in our laboratory, saponin was observed to induce extreme reticuloendothelial (RE) hypofunction. Possible RE blockade from saponin-induced hemolysis was suspected beside its toxic and suppressive effects on marrow RE activity. RE function was assessed with /sup 113m/In-ChS at various intervals after intravenous hemolysates in the rabbit by organ radioassay technic. The hemolysate resulted in immediate RE hypofunction, especially in the spleen and liver. Marrow RE suppression was visualized by marrow scanning. The hypofunction may result from phagocytosis ofmore » the ghost cells and homoglobin by cells of the RE organs; the saponin-induced marrow RE hypofunction, however, is much severer than this. The studies indicate that /sup 113m/In-ChS is especially suitable for assessment of the marrow RE activity and its imaging. (auth)« less

[Effect of intravenous treatment with OK-432 on the bone marrow in patients with lung cancer].

PubMed

Fujii, M; Ishikawa, M; Toki, H

1984-03-01

We studied effects of OK-432 on the bone marrow and peripheral blood cells of lung cancer patients. The nuclear cell count of bone marrow increased in 5 to 7 patients upon intravenous treatment with OK-432 compared with 3 of 6 patients who were intramuscularly treated with OK-432. Serial neutrophil counts of bone marrow increased in all 7 patients treated intravenously compared with 3 of 6 patients treated intramuscularly. The mean nuclear cell count or the serial neutrophil count of bone marrow in intravenously treated patients was significantly higher than the pretreatment values (p less than 0.001). In the peripheral blood picture, the difference in white blood cells or neutrophils before and after intravenous treatment was also statistically significant (p less than 0.01). There was no change in the erythrocytic series count of bone marrow and the hemoglobin count. Our results support the superiority of intravenous OK-432 treatment over intramuscular treatment in the growth-accelerating effect on bone marrow cells, especially regarding the neutrophil series.

Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.

PubMed

Engel, Barbara C; Podsakoff, Greg M; Ireland, Joanna L; Smogorzewska, E Monika; Carbonaro, Denise A; Wilson, Kathy; Shah, Ami; Kapoor, Neena; Sweeney, Mirna; Borchert, Mark; Crooks, Gay M; Weinberg, Kenneth I; Parkman, Robertson; Rosenblatt, Howard M; Wu, Shi-Qi; Hershfield, Michael S; Candotti, Fabio; Kohn, Donald B

2007-01-15

A patient with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells.

Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report

PubMed Central

Engel, Barbara C.; Podsakoff, Greg M.; Ireland, Joanna L.; Smogorzewska, E. Monika; Carbonaro, Denise A.; Wilson, Kathy; Shah, Ami; Kapoor, Neena; Sweeney, Mirna; Borchert, Mark; Crooks, Gay M.; Weinberg, Kenneth I.; Parkman, Robertson; Rosenblatt, Howard M.; Wu, Shi-Qi; Hershfield, Michael S.; Candotti, Fabio; Kohn, Donald B.

2007-01-01

A patient with adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells. PMID:16973956

The Analysis of the Adverse Reaction of Traditional Chinese Medicine Tumor Bone Marrow Suppression

NASA Astrophysics Data System (ADS)

Wei, Zhenzhen; Fang, Xiaoyan; Miao, Mingsan

2018-01-01

With the rapid increase of cancer patients, chemotherapy is the main method for the clinical treatment of cancer, but also in the treatment of the adverse reactions--bone marrow suppression is often a serious infection caused by patients after chemotherapy and the important cause of mortality. Chinese medicine has obvious advantages in the prevention and treatment of bone marrow depression after chemotherapy. According to tumor bone marrow suppression after chemotherapy of etiology and pathogenesis of traditional Chinese medicine and China national knowledge internet nearly 10 years of traditional Chinese medicine in the prevention and control of the status of clinical and laboratory research of tumor bone marrow suppression, the author analyzed and summarized its characteristics, so as to provide the basis for treating bone marrow suppression of drug research and development, and promote small adverse reactions of the development and utilization of natural medicine and its preparations.

A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow.

PubMed

Wynn, Robert F; Hart, Claire A; Corradi-Perini, Carla; O'Neill, Liam; Evans, Caroline A; Wraith, J Ed; Fairbairn, Leslie J; Bellantuono, Ilaria

2004-11-01

Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after transplantation, important for the correction of conditions such as metabolic storage disorders, can occur but with poor efficiency. Substantial improvements in engraftment will be required in order to derive a clinical benefit from MSC transplantation. Chemokines are the most important factors controlling cellular migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in promoting the migration of cells to the bone marrow, via its specific receptor CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its role in mediating migration to bone marrow. We show that CXCR4, although present at the surface of a small subset of MSCs, is important for mediating specific migration of these cells to bone marrow.

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Peter A.

For the purposes of making reliable first-principles predictions of defect energies in semiconductors, it is crucial to distinguish between effective-mass-like defects, which cannot be treated accurately with existing supercell methods, and deep defects, for which density functional theory calculations can yield reliable predictions of defect energy levels. The gallium antisite defect GaAs is often associated with the 78/203 meV shallow double acceptor in Ga-rich gallium arsenide. Within a conceptual framework of level patterns, analyses of structure and spin stabilization can be used within a supercell approach to distinguish localized deep defect states from shallow acceptors such as B As. Thismore » systematic approach determines that the gallium antisite supercell results has signatures inconsistent with an effective mass state and cannot be the 78/203 shallow double acceptor. Lastly, the properties of the Ga antisite in GaAs are described, total energy calculations that explicitly map onto asymptotic discrete localized bulk states predict that the Ga antisite is a deep double acceptor and has at least one deep donor state.« less

Distribution of major herbicides in ground water of the United States

USGS Publications Warehouse

Barbash, Jack E.; Thelin, Gail P.; Kolpin, Dana W.; Gilliom, Robert J.

1999-01-01

Frequencies of detection at or above 0.01 microgram per liter in shallow ground water beneath agricultural areas during the NAWQA study were significantly correlated with agricultural use in those areas for atrazine, cyanazine, alachlor, and metolachlor (P<0.05; Spearman rank correlations), but not for simazine (P>0.05). In urban areas, overall frequencies of detection of these five herbicides in shallow ground water were positively correlated with their total nonagricultural use nationwide (P=0.026; simple linear correlation). Multivariate statistical analysis indicated that frequencies of detection in shallow ground water beneath agricultural areas were positively correlated with half-lives for transformation in aerobic soil and agricultural use of the compounds (P≤0.0001 for both parameters). Although frequencies of detection were not significantly correlated with their subsurface mobility (Koc; P=0.19) or the median well depths of the sampled networks (P=0.72), the range of Koc values among the five herbicides and the range of well depths were limited.

Selective Resistance of CD44hi T Cells to p53 Dependent Cell Death Results in Persistence of Immunologic Memory after Total Body Irradiation1,2,3

PubMed Central

Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

2011-01-01

Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation (TLI) markedly changes the balance of residual T cell subsets to favor CD4+CD44hi natural killer T (NKT) cells due to differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results show that CD4+ T cells were markedly more resistant than CD8+ T cells, and CD44hi T cells including NKT cells and memory T cells were markedly more resistant than CD44lo (naïve) T cells. The memory T cells immunized to alloantigens persisted even after myeloabloative (1,000cGy) TBI, and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1,000cGy was prevented in p53−/− mice, there was progressive T cell death in p53−/− mice at higher doses. Whereas, p53 dependent T cell death changed the balance of subsets, the p53 independent T cell death did not. In conclusion, resistance of CD44hi T cells to p53 dependent cell death results in the persistence of immunological memory after TBI, and can explain the immune mediated rejection of marrow transplants in sensitized recipients. PMID:21930972

Histological features of bone marrow in paediatric patients during the asymptomatic phase of early-stage Black African sickle cell anaemia.

PubMed

Mauriello, Alessandro; Giacobbi, Erica; Saggini, Andrea; Isgrò, Antonella; Facchetti, Simone; Anemona, Lucia

2017-04-01

Bone marrow histological features of sickle cell anaemia (SCA) patients during early stages and in the asymptomatic phase of the disease appear an interesting area of study, representing early-stage consequences of SCA with a close relation to its pathophysiology. Unfortunately, this field of research has never been specifically addressed before. Bone marrow biopsies from 26 consecutive Black African SCA patients (M:F=1.6:1; age 2-17 years), free of clinical signs of chronic bone marrow damage, with no recent history of symptomatic vaso-occlusive episodes, and waiting for haematopoietic stem cell transplantation (HSCT), underwent morphological, immunohistochemical and electron microscopy evaluation. Additional comparison with three bone marrow specimens from post-HSCT SCA patients and 10 bone marrow specimens from AS healthy carriers was performed. Bone marrow of SCA patients was normocellular or slighly hypercellular in all cases. Erythroid hyperplasia was a common feature. Myeloid lineage was slightly decreased with normal to slightly diminished neutrophilic granulocytes; CD68 positive monocytic-macrophagic cells appeared slightly increased, with a predominant CD163 positive M2/M(Hb) phenotype. A positive correlation was found between haemoglobin values and number of bone marrow erythroid cells (R 2 =0.15, p=0.05). Intravascular and interstitial clusters of erythroid sickle cells were found in bone marrow of pre-HSCT homozygous SS SCA patients, as well as heterozygous AS healthy carriers, and the single post-HSCT patient matched to an AS health carrier donor. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Patterns of hemopoietic reconstitution in nonobese diabetic mice: dichotomy of allogeneic resistance versus competitive advantage of disease-resistant marrow.

PubMed

Kaufman, C L; Li, H; Ildstad, S T

1997-03-01

Complete replacement of the immune system via allogeneic bone marrow transplantation is sufficient to prevent diabetes in the nonobese diabetic (NOD) mouse model. In the present study we examined whether mixed allogeneic reconstitution would be sufficient to interrupt the autoimmune process with respect to occurrence of overt diabetes, as well as preexisting autoimmune insulitis. NOD mice were lethally irradiated and reconstituted with a mixture of NOD and B10.BR marrow. A relative resistance to allogeneic bone marrow engraftment was noted in NOD recipients of the mixed bone marrow inoculum, compared with disease-resistant controls. Moreover, unlike disease-resistant controls, all animals that initially repopulated as mixed donor/host chimeras became predominantly allogeneic by 4 mo, suggesting a competitive advantage for long term engraftment for disease-resistant marrow. All but one mouse in the group that engrafted with allogeneic marrow remained free of diabetes for the entire follow-up period (n = 22). Moreover, in all animals examined, virtually all islets were free of insulitis. In contrast, 74% of NOD mice that received similar conditioning and failed to engraft with donor marrow developed acute diabetes and intra-islet insulitis was present in all animals examined. These data suggest that NOD mice exhibit a relative resistance to engraftment compared with disease-resistant recipients. Conversely, animals that initially repopulated as a mixture of syngeneic and donor marrow become converted to virtually all donor by 4 mo. These data provide additional support that a defective stem cell is responsible for autoimmune diabetes in this experimental model.

Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma.

PubMed Central

Riccardi, A; Ucci, G; Luoni, R; Castello, A; Coci, A; Magrini, U; Ascari, E

1990-01-01

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance. Images PMID:2199532

Selective Shielding of Bone Marrow: An Approach to Protecting Humans from External Gamma Radiation.

PubMed

Waterman, Gideon; Kase, Kenneth; Orion, Itzhak; Broisman, Andrey; Milstein, Oren

2017-09-01

The current feasibility of protecting emergency responders through bone marrow selective shielding is highlighted in the recent OECD/NEA report on severe accident management. Until recently, there was no effective personal protection from externally penetrating gamma radiation. In Chernobyl, first-responders wore makeshift lead sheeting, whereas in Fukushima protective equipment from gamma radiation was not available. Older protective solutions that use thin layers of shielding over large body surfaces are ineffective for energetic gamma radiation. Acute exposures may result in Acute Radiation Syndrome where the survival-limiting factor up to 10 Gy uniform, homogeneous exposure is irreversible bone marrow damage. Protracted, lower exposures may result in malignancies of which bone marrow is especially susceptible, being compounded by leukemia's short latency time. This highlights the importance of shielding bone marrow for preventing both deterministic and stochastic effects. Due to the extraordinary regenerative potential of hematopoietic stem cells, to effectively prevent the deterministic effects of bone marrow exposure, it is sufficient to protect only a small fraction of this tissue. This biological principle allows for a new class of equipment providing unprecedented attenuation of radiation to select marrow-rich regions, deferring the hematopoietic sub-syndrome of Acute Radiation Syndrome to much higher doses. As approximately half of the body's active bone marrow resides within the pelvis region, shielding this area holds great promise for preventing the deterministic effects of bone marrow exposure and concomitantly reducing stochastic effects. The efficacy of a device that selectively shields this region and other radiosensitive organs in the abdominal area is shown here.

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

Missing Cells: Pathophysiology, Diagnosis, and Management of (Pan)Cytopenia in Childhood

PubMed Central

Erlacher, Miriam; Strahm, Brigitte

2015-01-01

Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings, such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia, whereas antibody-mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. By contrast, pancytopenia is frequently associated with a hypocellular bone marrow, and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita, and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition, and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC) can reliably be differentiated on a morphological level, the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC, and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pan)cytopenia, their pathophysiology, characteristic bone marrow findings, and therapeutic approaches. PMID:26217651

Dynamics of Internal Tides Over a Shallow Ridge Investigated With a High-Resolution Downscaling Regional Ocean Model

NASA Astrophysics Data System (ADS)

Masunaga, Eiji; Uchiyama, Yusuke; Suzue, Yota; Yamazaki, Hidekatsu

2018-04-01

This study investigates the dynamics of tidally induced internal waves over a shallow ridge, the Izu-Ogasawara Ridge off the Japanese mainland, using a downscaled high-resolution regional ocean numerical model. Both the Kuroshio and tides contribute to the field of currents in the study area. The model results show strong internal tidal energy fluxes over the ridge, exceeding 3.5 kW m-1, which are higher than the fluxes along the Japanese mainland. The flux in the upstream side of the Kuroshio is enhanced by an interaction of internal waves and currents. The tidal forcing induces 92% of the total internal wave energy flux, exhibiting the considerable dominance of tides in internal waves. The tidal forcing enhances the kinetic energy, particularly in the northern area of the ridge where the Kuroshio Current is not a direct influence. The tidal forcing contributes to roughly 30% of the total kinetic energy in the study area.

Aquatic Invertebrate Assemblages in Shallow Prairie Lakes: Fish and Environmental Influences

USGS Publications Warehouse

Paukert, C.P.; Willis, D.W.

2003-01-01

We sampled zooplankton and benthic macroinvertebrate assemblages in 30 shallow natural lakes to determine the effects of the environment (i.e., habitat and fish abundance) on invertebrates. Zooplankters were identified to genus, and up to 120 individuals per genus were measured. Macroinvertebrates were identified to order, class, or family. Fish communities were also sampled. Relative abundances of zooplankton and macroinvertebrates were low at increased chlorophyll a concentrations, although mean zooplankton length increased with total phosphorus, possibly because of an increased proportion of microzooplankton (rotifers and copepod nauplii) at higher phosphorus levels. Canonical correspondence analysis revealed that zooplankton and macroinvertebrate abundance was influenced by submersed vegetation coverage, whereas zooplankton abundance and size structure were also related to productivity (i.e., chlorophyll a and total phosphorus). However, relative abundance of fish species or fish feeding guilds was not strongly correlated with zooplankton or macroinvertebrate abundance or zooplankton size structure. Physical habitat (e.g., vegetation coverage) may exert substantial influences on invertebrate assemblages in these lakes, possibly providing a refuge from fish predation.

Effect of abalone farming on seawater movement and benthic foraminiferal assemblage of Zostera marina in the inner bay of Wando, South Korea.

PubMed

Lee, Yeon Gyu; Choi, Yang Ho; Jeong, Da Un; Lee, Jung Sick; Kim, Yong Wan; Park, Jung Jun; Choi, Jae Ung

2016-08-15

Tidal current survey as well as geochemical and benthic foraminiferal analyses of sediment cores were conducted in an abalone farm and a Zostera bed to understand the degree to which the abalone farm facilities installed along a channel in a shallow sea affect the benthic environment and ecology. In the abalone farm, Ammonia beccarii-Pseudoparrella naraensis-Elphidium somaense-Rosalina globularis-Trochammina hadai and P. naraensis-E. somaense-A. beccarii-T. hadai assemblages appeared owing to an increase in the total nitrogen content from the biodeposits. The Zostera bed consisted of A. beccarii-P. naraensis-Buccella frigida-T. hadai assemblage owing to the gradual expansion of a brackish shallow-water environment by the rapidly decreasing current speed, and it may have flourished. Moreover, the total sulfur, Zn, Cr, and Cu contents in the sediments decreased remarkably more than those of the pre-abalone farming did, caused by the vigorous activity of Zostera marina physiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Total Suspended Matter (TSM) and Maximum Signal Depth (Z90_max) for Monitoring the Evolution of Sediment Resuspension Process in Shallow Coastal Environments

NASA Astrophysics Data System (ADS)

Filipponi, Federico; Zucca, Francesco; Taramelli, Andrea; Valentini, Emiliana

2015-12-01

Monitoring sediment fluxes patterns in coastal area, like dispersion, sedimentation and resuspension processes, is a relevant topic for scientists, decision makers and natural resources management. Time series analysis of Earth Observation (EO) data may contribute to the understanding and the monitoring of processes in sedimentary depositional marine environment, especially for shallow coastal areas. This research study show the ability of optical medium resolution imagery to interpret the evolution of sediment resuspension from seafloor in coastal areas during intense wind forcings. Intense bora wind events in northern Adriatic Sea basin during winter season provoke considerable wave-generated resuspension of sediments, which cause variation in water column turbidity. Total Suspended Matter (TSM) product has been selected as proxy for qualitative and quantitative analysis of resuspended sediments. In addition, maximum signal depth (Z90_max), has been used to evaluate the evolution of sediment concentration in the water column.

Sedimentary hydrocarbons and sterols in a South Atlantic estuarine/shallow continental shelf transitional environment under oil terminal and grain port influences.

PubMed

Bet, Rafael; Bícego, Marcia C; Martins, César C

2015-06-15

Sterols and hydrocarbons were determined in the surface sediments from the transitional environment between Paranaguá Bay and the shallow continental shelf in the South Atlantic to assess the sources of organic matter (OM) and the contamination status of an area exposed to multiple anthropogenic inputs. Total aliphatic hydrocarbon concentrations were less than 10μgg(-1), which is typical of unpolluted sediments, and related to recent inputs from higher terrestrial plants. Total polycyclic aromatic hydrocarbon ranged from

Bone Marrow Diseases

MedlinePlus

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

Bone Marrow Transplantation

MedlinePlus

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

Bone marrow biopsy

MedlinePlus

... aspiration removes a small amount of marrow in liquid form for examination. ... and a syringe is used to withdraw the liquid bone marrow. If this is done, the needle will be removed and repositioned. Or, another needle may be used for the biopsy.

Additional Sediment/Soil Sampling Conducted at the Little Sioux Bend Shallow Water Habitat Project Site during October 2013

DTIC Science & Technology

2013-11-01

Conditions in the Missouri River and Gulf of Mexico ................................................43 4.3 Comparison of Total Phosphorus Levels...Sediment Management” which assessed nutrient loadings to the Missouri River and Gulf of Mexico (NRC, 2011). The report concluded that potential...concern regarding Gulf of Mexico hypoxia. Currently, the total phosphorus load to the Gulf of Mexico is estimated to be 154,300 metric tons per year

Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow.

PubMed Central

Irons, R D

1981-01-01

A detailed description of flow cytofluorometric DNA cell cycle analysis is presented. A number of studies by the author and other investigators are reviewed in which a method is developed for the analysis of cell cycle phase in bone marrow of experimental animals. Bone marrow cell cycle analysis is a sensitive indicator of changes in bone marrow proliferative activity occurring early in chemically-induced myelotoxicity. Cell cycle analysis, used together with other hematologic methods, has revealed benzene-induced toxicity in proliferating bone marrow cells to be cycle specific, appearing to affect a population in late S phase which then accumulate in G2/M. PMID:7016521

The diagnostic utility of bone marrow aspiration and biopsy in patients with acquired immunodeficiency syndrome.

PubMed

Gluckman, R J; Rosner, F; Guarneri, J J

1989-02-01

Diagnostic bone marrow aspiration, biopsy, and culture are useful procedures in the evaluation of patients with suspected or proven acquired immunodeficiency syndrome (AIDS) who are febrile. In as many as one fourth of these patients, the information provided by the bone marrow examination may establish a diagnosis of a disseminated opportunistic infection when other studies are not informative. We have also discovered a previously unreported association between thrombocytopenia and the presence of bone marrow granulomas in our patients with AIDS and suggest that thrombocytopenia may be a clue to enable the clinician to predict a positive bone marrow result more accurately. The explanation for this apparent association remains to be elucidated.

Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

PubMed

Gil-Sanchis, Claudia; Cervelló, Irene; Khurana, Satish; Faus, Amparo; Verfaillie, Catherine; Simón, Carlos

2015-06-01

To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation. Prospective experimental animal study. University research laboratories. β-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice. The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP(+) cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4(-)BM-MAPCs), BMDC hypoblast-like stem cells (mOct4(+) BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice. Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis. After 12 weeks, histologic analysis revealed that uteri of mice with mOct4(-)BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4(+) BM-HypoSCs. The percentage of engrafted GFP(+) cells ranged from 0.13%-4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL(+) cells were increased in the EPCs and mOct4(+)BM-HypoSCs groups. Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4(+) BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4(-)BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.

2012-11-01

Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hoursmore » before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the harmful effects of LDR radiation.« less

Interferon regulatory factor 4 (IRF4) controls myeloid-derived suppressor cell (MDSC) differentiation and function.

PubMed

Nam, Sorim; Kang, Kyeongah; Cha, Jae Seon; Kim, Jung Woo; Lee, Hee Gu; Kim, Yonghwan; Yang, Young; Lee, Myeong-Sok; Lim, Jong-Seok

2016-12-01

Myeloid-derived suppressor cells (MDSCs) are immature cells that do not differentiate into mature myeloid cells. Two major populations of PMN-MDSCs (Ly6G high Ly6C low Gr1 high CD11b + ) and MO-MDSCs (Ly6G - Ly6C high Gr-1 int CD11b + ) have an immune suppressive function. Interferon regulatory factor 4 (IRF4) has a role in the negative regulation of TLR signaling and is associated with lymphoid cell development. However, the roles of IRF4 in myeloid cell differentiation are unclear. In this study, we found that IRF4 expression was remarkably suppressed during the development of MDSCs in the tumor microenvironment. Both the mRNA and protein levels of IRF4 in MDSCs were gradually reduced, depending on the development of tumors in the 4T1 model. siRNA-mediated knockdown of IRF4 in bone marrow cells promoted the differentiation of PMN-MDSCs. Similarly, IRF4 inhibition in bone marrow cells using simvastatin, which has been known to inhibit IRF4 expression, increased PMN-MDSC numbers. In contrast, IRF4 overexpression in bone marrow cells inhibited the total numbers of MDSCs, especially PMN-MDSCs. Notably, treatment with IL-4, an upstream regulator of IRF4, induced IRF4 expression in the bone marrow cells, and consequently, IL-4-induced IRF4 expression resulted in a decrease in PMN-MDSC numbers. Finally, we confirmed that IRF4 expression in MDSCs can modulate their activity to inhibit T cell proliferation through IL-10 production and ROS generation, and myeloid-specific deletion of IRF4 leads to the increase of MDSC differentiation. Our present findings indicate that IRF4 reduction induced by tumor formation can increase the number of MDSCs, and increases in the IRF4 expression in MDSCs may infringe on the immune-suppressive function of MDSCs. © Society for Leukocyte Biology.

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 the PTV length exceeds the bed travel distance. In this work, the dosimetric challenges associated with junctioning longitudinally adjacent PTVs with HT were analyzed and the feasibility of PTV junctioning was demonstrated. The benefits of spatially dividing or splitting the treatment into a few sub-treatments along the longitudinal direction were also investigated.

Automated morphological analysis of bone marrow cells in microscopic images for diagnosis of leukemia: nucleus-plasma separation and cell classification using a hierarchical tree model of hematopoesis

NASA Astrophysics Data System (ADS)

Krappe, Sebastian; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

2016-03-01

The morphological differentiation of bone marrow is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually under the use of bright field microscopy. This is a time-consuming, subjective, tedious and error-prone process. Furthermore, repeated examinations of a slide may yield intra- and inter-observer variances. For that reason a computer assisted diagnosis system for bone marrow differentiation is pursued. In this work we focus (a) on a new method for the separation of nucleus and plasma parts and (b) on a knowledge-based hierarchical tree classifier for the differentiation of bone marrow cells in 16 different classes. Classification trees are easily interpretable and understandable and provide a classification together with an explanation. Using classification trees, expert knowledge (i.e. knowledge about similar classes and cell lines in the tree model of hematopoiesis) is integrated in the structure of the tree. The proposed segmentation method is evaluated with more than 10,000 manually segmented cells. For the evaluation of the proposed hierarchical classifier more than 140,000 automatically segmented bone marrow cells are used. Future automated solutions for the morphological analysis of bone marrow smears could potentially apply such an approach for the pre-classification of bone marrow cells and thereby shortening the examination time.

Bone marrow solid core biopsy needle: a critical assessment of the utility, benefits and limitations of the instruments employed in current day haematology and oncology.

PubMed

Islam, Anwarul

2018-06-01

The optimal clinical evaluation of the bone marrow requires an examination of air-dried and well-stained films of the aspirated tissue along with a histopathological evaluation of adequately processed and properly stained core biopsy specimens. A bone marrow evaluation can be essential in establishing a diagnosis, determining the efficacy of treatment in haematological disorders and to monitor haematological status of patients following bone marrow/stem cell transplantation. It is also an essential component of the staging process for newly diagnosed malignancies. Currently available bone marrow aspiration needles are quite satisfactory and if properly used provide good-quality specimens for morphological evaluation. However, if a bone marrow core biopsy is concerned, several needles are currently in use but not all of them provide good-quality biopsy specimens for histological evaluation or are user friendly. We have compared the recently introduced Moeller Medical single use bone marrow core biopsy needle with the Jamshidi needle with marrow acquisition cradle (CareFusion), J-needle (Cardinal Health) and OnControl device (Vidacare). It is concluded that the Moeller Medical needle system has definite advantages over others and is recommended for routine use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia].

PubMed

Tanabe, Y; Dan, K; Kuriya, S; Nomura, T

1989-10-01

The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

Mesenchymal stromal cell derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells

PubMed Central

Wen, Sicheng; Dooner, Mark; Cheng, Yan; Papa, Elaine; Del Tatto, Michael; Pereira, Mandy; Deng, Yanhui; Goldberg, Laura; Aliotta, Jason; Chatterjee, Devasis; Stewart, Connor; Carpanetto, Andrea; Collino, Federica; Bruno, Stefania; Camussi, Giovanni; Quesenberry, Peter

2016-01-01

Mesenchymal stromal cells (MSC) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 hours to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 hours post-irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow. The murine hematopoietic cell line, FDC-P1 exposed to 500 cGy, showed reversal of growth inhibition, DNA damage and apoptosis on exposure to murine or human MSC-EVs. Both murine and human MSC-EVs reverse radiation damage to murine marrow cells and stimulate normal murine marrow stem cell/progenitors to proliferate. A preparation with both exosomes and microvesicles was found to be superior to either microvesicles or exosomes alone. Biologic activity was seen in freshly isolated vesicles and in vesicles stored for up to 6 months in 10% DMSO at −80°C. These studies indicate that MSC-EVs can reverse radiation damage to bone marrow stem cells. PMID:27150009

Bone Marrow Aspirate Concentrate in Combination With Intravenous Iloprost Increases Bone Healing in Patients With Avascular Necrosis of the Femoral Head: A Matched Pair Analysis.

PubMed

Pilge, Hakan; Bittersohl, Bernd; Schneppendahl, Johannes; Hesper, Tobias; Zilkens, Christoph; Ruppert, Martin; Krauspe, Rüdiger; Jäger, Marcus

2016-11-17

With disease progression, avascular necrosis (AVN) of the femoral head may lead to a collapse of the articular surface. The exact pathophysiology of AVN remains unclear, although several conditions are known that can result in spontaneous cell death, leading to a reduction of trabecular bone and the development of AVN. Hip AVN treatment is stage-dependent in which two main stages of the disease can be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV, crescent sign). In the pre-collapse phase, core decompression (CD), with or without the addition of bone marrow ( e.g . bone marrow aspirate concentrate, BMAC) or bone graft, is a common treatment alternative. In the post-collapse phase, THA (total hip arthroplasty) must be performed in most of the patients. In addition to surgical treatment, the intravenous application of Iloprost has been shown to have a curative potential and analgesic effect. From October 2009 to October 2014, 49 patients with AVN (stages I-III) were treated with core decompression at our institution. All patients were divided into group A (CD + BMAC) and group B (CD alone). Of these patients, 20 were included in a matched pair analysis. The patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle d'Aubigné Score and the Kerboul combined necrotic angle in a-p and lateral radiographs were evaluated pre- and postoperatively. The primary endpoint was a total hip arthroplasty. In group A, two patients needed THA while in group B four patients were treated with THA. In group A, the Merle d'Aubigné Score improved from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no difference between the pre- (14.3) and postoperative (14.1) assessment. The mean of the Kerboul angle showed no difference in both groups compared pre- to postoperatively (group A: pre-op 212°, postop 220°, group B: pre-op 213, postop 222°). Regarding radiographic evaluation, the interobserver variability revealed a moderate agreement between two raters regarding the pre-(ICC 0.594) and postoperative analysis (ICC 0.604).This study demonstrates that CD in combination with the application of autologous bone marrow aspirate concentrate into the femoral head seems to be a safe and efficient treatment alternative in the early stages of AVN of the femoral head when compared to CD alone.

Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Jeffrey Y.C., E-mail: jwong@coh.org; Forman, Stephen; Somlo, George

2013-01-01

Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamidemore » (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to dose-limiting toxicities. Future efforts will focus on whether further dose escalation with CY/VP16 is safe, with the goal of improving disease control in this high-risk population.« less

Reusable Reinforcement Learning via Shallow Trails.

PubMed

Yu, Yang; Chen, Shi-Yong; Da, Qing; Zhou, Zhi-Hua

2018-06-01

Reinforcement learning has shown great success in helping learning agents accomplish tasks autonomously from environment interactions. Meanwhile in many real-world applications, an agent needs to accomplish not only a fixed task but also a range of tasks. For this goal, an agent can learn a metapolicy over a set of training tasks that are drawn from an underlying distribution. By maximizing the total reward summed over all the training tasks, the metapolicy can then be reused in accomplishing test tasks from the same distribution. However, in practice, we face two major obstacles to train and reuse metapolicies well. First, how to identify tasks that are unrelated or even opposite with each other, in order to avoid their mutual interference in the training. Second, how to characterize task features, according to which a metapolicy can be reused. In this paper, we propose the MetA-Policy LEarning (MAPLE) approach that overcomes the two difficulties by introducing the shallow trail. It probes a task by running a roughly trained policy. Using the rewards of the shallow trail, MAPLE automatically groups similar tasks. Moreover, when the task parameters are unknown, the rewards of the shallow trail also serve as task features. Empirical studies on several controlling tasks verify that MAPLE can train metapolicies well and receives high reward on test tasks.

Biodiversity of shallow subtidal, under-rock invertebrates in Europe's first marine reserve: Effects of physical factors and scientific sampling

NASA Astrophysics Data System (ADS)

Trowbridge, Cynthia D.; Kachmarik, Katy; Plowman, Caitlin Q.; Little, Colin; Stirling, Penny; McAllen, Rob

2017-03-01

At Lough Hyne Marine Reserve in SW Ireland, shallow subtidal, under-rock biodiversity was investigated to assess (i) any deleterious effects of scientific sampling and (ii) quantitative baseline community patterns. Comparisons were made between 10 sites with annual rock-turning disturbance and 10 with multi-decadal (historical) disturbance. At each site, shallow subtidal rocks (N = 1289 total) were lifted, organisms recorded, and rocks replaced in their original position. Biodiversity indices were calculated to evaluate how diversity varied with location within the lough, frequency of sampling disturbance, degree of hypoxia/anoxia, dissolved oxygen (DO) concentration, and number of rocks turned. The richness of solitary invertebrates surveyed in situ averaged 21 taxa per site with significantly more in the South Basin (near the lough's connection to the ocean) than in the North Basin. The Shannon-Wiener Index did not differ significantly with variables investigated. However, evenness was higher at annually disturbed sites than at historical ones where anemones with algal symbionts often dominated. Several sites were hypoxic to anoxic under the shallow subtidal rocks. Cup corals were most abundant in the South Basin; DO was a crucial explanatory variable of these sensitive species. Solitary ascidians were most abundant at South-Basin annual sites with DO levels being a highly significant explanatory variable.

α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frost, Sophia; Miller, Brian W.; Back, Tom

Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i.more » Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.« less

Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

PubMed

Eapen, Mary; Raetz, Elizabeth; Zhang, Mei-Jie; Muehlenbein, Catherine; Devidas, Meenakshi; Abshire, Thomas; Billett, Amy; Homans, Alan; Camitta, Bruce; Carroll, William L; Davies, Stella M

2006-06-15

The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI)-containing transplant regimens (relative risk [RR], 0.49; 95% confidence interval [CI] 0.33-0.71, P < .001) than chemotherapy regimens. In contrast, for children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.

National Hematopoietic Stem Cells Transplant Registry in Poland: Nationwide Internet Reporting System and Results.

PubMed

Łęczycka, A; Dudkiewicz, M; Czerwiński, J; Malanowski, P; Żalikowska-Hołoweńko, J; Danielewicz, R

2016-06-01

History of hematopoietic stem cell transplantations in Poland begins in early 1980s; the 1st bone marrow allotransplantation was performed in 1983 in the Central Clinical Hospital of the Military Medical Academy in Warsaw. Following years brought the 1st autologous stem cell transplantations. Ten years later, unrelated bone marrow transplantation was performed for the 1st time by the team of the Hematology and Blood and Marrow Transplantation Unit in Katowice. Since then, hematopoietic stem cell transplantation developed to be standard procedure and one of the most important therapies applied in leukemia treatment. The number of allotransplantations in Poland has grown significantly in the past 2 decades, which generated new needs and problems. In 2005, based on a new Transplant Law, a National Transplants Registry was created. Its main role is to collect data (registration of procedures and follow-up data) related to every transplantation case for stem cells and tissues as well as for organs. We present statistics concerning stem cell transplantations performed in Poland, as collected in the National Transplants Registry in the years 2006-2014. There are 18 centers transplanting hematopoietic stem cells in Poland. The total number of hematopoietic stem cell transplantations performed in 2006-2014 was 3,537, with allotransplantations from relatives accounted for 1,491 and from unrelated donors for 2,046. The main indication for allotransplantation in past years was acute leukemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse.

PubMed

Lin, K H; Jou, S T; Chen, R L; Lin, D T; Lui, L T; Lin, K S

1994-01-01

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.

The hollow fiber bioreactor as a stroma-supported, serum-free ex vivo expansion platform for human umbilical cord blood cells.

PubMed

Xue, Cao; Kwek, Kenneth Y C; Chan, Jerry K Y; Chen, Qingfeng; Lim, Mayasari

2014-07-01

The bone marrow microenvironment plays an integral role in the regulation of hematopoiesis. Residing stromal cells and the extracellular matrix in the bone marrow microenvironment provide biological signals that control hematopoietic stem cell (HSC) function. In this study, we developed a bio-mimetic co-culture platform using the hollow fiber bioreactor (HFBR) for ex vivo expansion of HSCs. We evaluated the efficacy of such a platform in comparison to standard cultures performed on tissue culture polystyrene (TCP), using a human stromal cell line (HS-5) as stromal support, co-cultured with lineage-depleted human cord blood cells in serum-free medium supplemented with a cytokine cocktail. Our results showed that the performance of the HFBR in supporting total cell and CD34(+) progenitor cell expansion was comparable to that of cultures on TCP. Cells harvested from the HFBR had a higher clonogenic ability. The performance of ex vivo-expanded cells from the HFBR in hematopoietic reconstitution in humanized mice was comparable to that of the TCP control. Scanning electron microscopy revealed that stroma cell growth inside the HFBR created a three-dimensional cell matrix architecture. These findings demonstrate the feasibility of utilizing the HFBR for creating a complex cell matrix architecture, which may provide good in vitro mimicry of the bone marrow, supporting large-scale expansion of HSCs. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bone marrow derived M2 macrophages protected against lipopolysaccharide-induced acute lung injury through inhibiting oxidative stress and inflammation by modulating neutrophils and T lymphocytes responses.

PubMed

Wang, Fang; Fu, Xiazhen; Wu, Xinwan; Zhang, Jianhai; Zhu, Jiali; Zou, Yun; Li, Jinbao

2018-06-05

Acute lung injury (ALI) is characterized by aggravated inflammatory responses and the subsequent alveolar-capillary injury for which there are no specific therapies available currently. The present study was designed to investigate the protective roles of bone marrow derived M 2 macrophages (M 2 BMDMs) in lipopolysaccharide (LPS) induced ALI. M 2 BMDMs were obtained from bone marrow cells stimulated with M-CSF and IL-4. Mice received M 2 BMDMs intratracheally 3 h after LPS administration. Histology and wet/dry (W/D) weight ratio, activated immune cells and total protein were detected. Cytokines production were measured in vivo and vitro study. The effects of PD-L1 blockade on M 2 BMDMs were calculated. The results showed that M 2 BMDMs administration reduced the infiltration of neutrophils, inhibited the oxidative stress, while increased the counts of CD3 + T lymphocytes as well as CD4 + CD25 + regulatory T lymphocytes. Further, M 2 BMDMs suppressed the TNF-α, IL-1β and IL-6 production, while increased the IL-10 production. Blockade of PD-L1/PD-1 pathway reversed cytokines production of M 2 BMDMs in the BALF. These findings indicated that M 2 BMDMs might be a promising therapeutic strategy for LPS-induced ALI through inhibiting oxidative stress and inflammation by modulating neutrophils and T lymphocytes responses. Copyright © 2018 Elsevier B.V. All rights reserved.

Interleukin-3 Does Not Affect the Differentiation of Mast Cells Derived from Human Bone Marrow Progenitors

PubMed Central

Shimizu, Yuji; Matsumoto, Kenji; Okayama, Yoshimichi; Kentaro, Sakai; Maeno, Toshitaka; Suga, Tatsuo; Miura, Toru; Takai, Shinji; Kurabayashi, Masahiko; Saito, Hirohisa

2008-01-01

Although IL-3 is commonly used for culture of human progenitor-derived mast cells together with Stem cell factor (SCF) and IL-6, the effect of IL-3 on human mast cell differentiation has not been well elucidated. Human bone marrow CD34+ progenitors were cultured for up to 12 weeks in the presence of rhSCF and rhIL-6 either with rhIL-3 (IL-3 (+)) or without rhIL-3 (IL-3 (−)) for the initial 1-week of culture. Total cell number increased at 2 weeks in IL-3 (+), as compared to IL-3 (−), but changes in the appearance of mast cells were delayed. When IL-3 was present for the initial 1-week culture, granules looked more mature with IL-3 than without IL-3. However, tryptase and chymase contents, and surface antigen expression (CD18, CD51, CD54, and CD117) were not altered by IL-3. Surface expression and mRNA level of FcεRIα and histamine release by crosslinking of FcεRIα did not differ from one preparation to the next. GeneChip analysis revealed that no significant differences were observed between IL-3 (+) and IL-3 (−) cells either when inactivated or activated by aggregation of FcεRIα. These findings indicate that initial incubation of human bone marrow CD34+ progenitors with IL-3 does not affect the differentiation of mast cells. PMID:18214796

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

PubMed Central

Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

2012-01-01

Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

Serious neutropenia following etanercept administration in a 62 years female patient of rheumatoid arthritis.

PubMed

Datta, K; Ghosh, R K; Ghosh, S M

2010-10-01

Tumor necrosis factor (TNF) plays an important role in the inflammatory process of RA and the resulting joint pathology. Etanercept is a member of anti TNF family which is indicated in patients with moderate to severe active rheumatoid arthritis either alone or in combination with MTX. Very few cases of neutropenia with etanercept treatment have been reported worldwide so far. The mechanism of etanercept induced neutropenia is not yet established. We report a case of 62 year female patient, developing etanercept induced neutropenia after 1 month of starting treatment. The absolute neutrophil count (ANC) came down to 150/microl on the 6th day of diagnosis. Bone marrow examination revealed a maturation arrest of granulocytic cells. Other marrow components were normal. Causality assessment of adverse drug reactions was done as per Naranjo's Algorithm. It was a probable ADR. We propose the possible mechanism of neutropenia is bone marrow toxicity. This is contrary to a previous case report which suggested peripheral consumption of neutrophil as a cause of neutropenia. Recently, there are some reports of leukemia and other hematological malignancies associated with the use of etanercept and in those conditions neutropenia could be the first manifestation. Neither product label of the drug nor US FDA warns for periodic blood investigation during etanercept therapy. There is a definite need for total and differential count estimation at the beginning and regular interval during etanercept treatment to rule out possibilities of neutropenia.

Impaired immune function in children and adults with Fanconi anemia.

PubMed

Myers, Kasiani C; Sauter, Sharon; Zhang, Xue; Bleesing, Jacob J; Davies, Stella M; Wells, Susanne I; Mehta, Parinda A; Kumar, Ashish; Marmer, Daniel; Marsh, Rebecca; Brown, Darron; Butsch Kovacic, Melinda

2017-11-01

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4 + T cells were decreased (P = 0.022), while CD8 + T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8 + T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development. © 2017 Wiley Periodicals, Inc.

Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury

PubMed Central

Porter, Rebecca L.; Georger, Mary; Bromberg, Olga; McGrath, Kathleen E.; Frisch, Benjamin J.; Becker, Michael W.; Calvi, Laura M.

2013-01-01

Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all mature blood cells, are regulated within the marrow microenvironment. We previously reported that pharmacologic treatment of naïve mice with prostaglandin E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this expansion remain unknown. Here we demonstrate that PGE2 treatment in naïve mice inhibits apoptosis of HSPCs without changing their proliferation rate. In a murine model of sub-lethal total body irradiation (TBI), in which HSPCs are rapidly lost, treatment with a long-acting PGE2 analogue (dmPGE2) reversed the apoptotic program initiated by TBI. dmPGE2 treatment in vivo decreased the loss of functional HSPCs following radiation injury, as demonstrated both phenotypically and by their increased reconstitution capacity. The antiapoptotic effect of dmPGE2 on HSPCs did not impair their ability to differentiate in vivo, resulting instead in improved hematopoietic recovery after TBI. dmPGE2 also increased microenvironmental cyclooxygenase-2 expression and expanded the α-SMA+ subset of marrow macrophages, thus enhancing the bone marrow microenvironmental response to TBI. Therefore, in vivo treatment with PGE2 analogues may be particularly beneficial to HSPCs in the setting of injury by targeting them both directly and also through their niche. The current data provide rationale for in vivo manipulation of the HSPC pool as a strategy to improve recovery after myelosuppression. PMID:23169593

The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

PubMed Central

Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

2012-01-01

The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

Epigenetic and microenvironmental alterations in bone marrow associated with ROS in experimental aplastic anemia.

PubMed

Chatterjee, Ritam; Law, Sujata

2018-01-01

Aplastic anemia or bone marrow failure often develops as an effect of chemotherapeutic drug application for the treatment of various pathophysiological conditions including cancer. The long-term bone marrow injury affects the basic hematopoietic population including hematopoietic stem/progenitor cells (HSPCs). The present study aimed in unearthing the underlying mechanisms of chemotherapeutics mediated bone marrow aplasia with special focus on altered redox status and associated effects on hematopoietic microenvironment and epigenetic status of hematopoietic cells. The study involves the development of busulfan and cyclophosphamide mediated mouse model for aplastic anemia, characterization of the disease with blood and marrow analysis, cytochemical examinations of bone marrow, flowcytometric analysis of hematopoietic population and microenvironmental components, determination of ROS generation, apoptosis profiling, expressional studies of Notch-1 signaling cascade molecules, investigation of epigenetic modifications including global CpG methylation of DNA, phosphorylation of histone-3 with their effects on bone marrow kinetics and expressional analysis of the anti-oxidative molecules viz; SOD-2 and Sdf-1. Severe hematopoietic catastrophic condition was observed during aplastic anemia which involved peripheral blood pancytopenia, marrow hypocellularity and decreased hematopoietic stem/progenitor population. Generation of ROS was found to play a central role in the cellular devastation in aplastic marrow which on one hand can be correlated with the destruction of hematopoiesis supportive niche components and alteration of vital Notch-1 signaling and on other hand was found to be associated with the epigenetic chromatin modifications viz; global DNA CpG hypo-methylation, histone-3 phosphorylation promoting cellular apoptosis. Decline of anti-oxidant components viz; Sdf-1 and SOD-2 hinted towards the irreversible nature of the oxidative damage during marrow aplasia. Collectively, the findings hinted towards the mechanistic correlation among ROS generation, microenvironmental impairment and epigenetic alterations that led to hematopoietic catastrophe under aplastic stress. The findings may potentiate successful therapeutic strategy development for the dreadful condition concerned. Copyright © 2017 Elsevier GmbH. All rights reserved.

Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group.

PubMed

Burchill, Susan A; Beiske, Klaus; Shimada, Hiroyuki; Ambros, Peter F; Seeger, Robert; Tytgat, Godelieve A M; Brock, Penelope R; Haber, Michelle; Park, Julie R; Berthold, Frank

2017-04-01

The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine-biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design. Cancer 2017;123:1095-1105. © 2016 American Cancer Society. © 2016 American Cancer Society.

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

PubMed

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

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 absorbed fraction method of dose calculation.

Comparison of fish catches with buoyant pop nets and seines in vegetated and nonvegetated habitats

USGS Publications Warehouse

Dewey, M.R.; Holland-Bartels, L. E.; Zigler, S.J.

1989-01-01

Two models of pop nets were developed to sample fish in shallow riverine waters, one for use in vegetated areas and the other for nonvegetated areas. Both nets have a mechanical release mechanism that can be tripped from the water surface. Replicated field tests were conducted to compare pop-net catches with bag-seine collections every 2 weeks from May through mid-October. Overall, total catch per effort did not vary significantly (P 2) was smaller than the area swept by the average seine haul (70-140 m2). The pop net effectively sampled fish in shallow nonvegetated habitats and was useful in heavily vegetated areas where seining or electroshocking was difficult.

Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

PubMed

Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

2015-06-01

Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

Influence of clinical status and parasite load on erythropoiesis and leucopoiesis in dogs naturally infected with leishmania (Leishmania) chagasi.

PubMed

Trópia de Abreu, Raquel; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Coura-Vital, Wendel; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

2011-05-10

The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL.

Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi

PubMed Central

Trópia de Abreu, Raquel; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Coura-Vital, Wendel; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

2011-01-01

Background The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). Methodology/Principal Findings The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Conclusions Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL. PMID:21572995

Cell Cycle Related Differentiation of Bone Marrow Cells into Lung Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dooner, Mark; Aliotta, Jason M.; Pimental, Jeffrey

2007-12-31

Green-fluorescent protein (GFP) labeled marrow cells transplanted into lethally irradiated mice can be detected in the lungs of transplanted mice and have been shown to express lung specific proteins while lacking the expression of hematopoietic markers. We have studied marrow cells induced to transit cell cycle by exposure to IL-3, IL-6, IL-11 and steel factor at different times of culture corresponding to different phases of cell cycle. We have found that marrow cells at the G1/S interface have a 3-fold increase in cells which assume a lung phenotype and that this increase is no longer seen in late S/G2. Thesemore » cells have been characterized as GFP{sup +} CD45{sup -} and GFP{sup +} cytokeratin{sup +}. Thus marrow cells with the capacity to convert into cells with a lung phenotype after transplantation show a reversible increase with cytokine induced cell cycle transit. Previous studies have shown the phenotype of bone marrow stem cells fluctuates reversibly as these cells traverse cell cycle, leading to a continuum model of stem cell regulation. The present studies indicate that marrow stem cell production of nonhematopoietic cells also fluctuates on a continuum.« less

Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

2011-01-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

PubMed

Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

2011-02-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.