WorldWideScience

Sample records for multiple foci bone

  1. Multiple coaxial foci generation by phase-only pupil filters

    Science.gov (United States)

    Valle, Pedro J.; Oti, José E.; Canales, Vidal F.; Cagigal, Manuel P.

    2007-04-01

    A new procedure for creating simultaneous multiple foci along the same optical axis with phase-only pupil-plane filters is proposed. Pupil-plane filters consist in phase-only masks described by simple circularly symmetric analytical functions. The axial separation between foci and their energy distribution are independently controlled by two different parameters of the filter. The main advantage of this new design is that, unlike other methods that required slow iterative algorithms, the proposed phase masks are straightforwardly calculated from analytical expressions. Moreover, real-time dynamic foci control could be achieved by using a computer addressed spatial light modulator that allowed the generation of variable phase patterns. The phase profiles we propose can be combined with multiple transversal foci phase patterns to actually form axial replicas of the transversal foci. Thus, it should be expected that three-dimensional structures were dynamically driven fast enough to perform real-time interactive multiple foci manipulation. Experimental verification of the multiple coaxial foci creation by static phase filters is shown.

  2. Creation of multiple on-axis foci and ultra-long focal depth for SPPs.

    Science.gov (United States)

    Wang, Jiayuan; Chen, Cuiyun; Sun, Zhijun

    2017-01-23

    We present the design of a plasmonic lens (PL) which is composed of pixelated nano-grooves on a gold film for the coupling and focusing of surface plasmon polaritons (SPPs) into multiple focal spots on the optical axis. The pixelated grooves are arranged along the y-axis and the x-position of each groove is optimized by the simulated annealing algorithm. PLs that implement two and three on-axis foci are presented and the designed structures have been validated with FDTD simulations. We also successfully constructed a long-focal-depth PL with a longitudinal FWHM of the focus that reached 25 plasmonic wavelengths, while its transverse field profile is maintained over 15 µm distance. The presented design method constitutes a new basis for plasmonic beam engineering, and the proposed particular SPP focal fields have potential applications in multiple imaging, particle manipulating, and plasmonic on-chip signal transmission.

  3. Controllable design of super-oscillatory lenses with multiple sub-diffraction-limit foci.

    Science.gov (United States)

    Li, Muyuan; Li, Wenli; Li, Haoyong; Zhu, Yechuan; Yu, Yiting

    2017-05-02

    The conventional multifocal optical elements cannot precisely control the focal number, spot size, as well as the energy distribution in between. Here, the binary amplitude-type super-oscillatory lens (SOL) is utilized, and a robust and universal optimization method based on the vectorial angular spectrum (VAS) theory and the genetic algorithm (GA) is proposed, aiming to achieve the required focusing performance with arbitrary number of foci in preset energy distribution. Several typical designs of multifocal SOLs are demonstrated. Verified by the finite-difference time-domain (FDTD) numerical simulation, the designed multifocal SOLs agree well with the specific requirements. Moreover, the full-width at half-maximum (FWHM) of the achieved focal spots is close to λ/3 for all the cases (λ being the operating wavelength), which successfully breaks the diffraction limit. In addition, the designed SOLs are partially insensitive to the incident polarization state, functioning very well for both the linear polarization and circular polarization. The optimization method presented provides a useful design strategy for realizing a multiple sub-diffraction-limit foci field of SOLs. This research can find its potentials in such fields as parallel particle trapping and high-resolution microscopy imaging.

  4. Imaging and clinical characteristics of children with multiple foci of microsusceptibility changes in the brain on susceptibility-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Aida, Noriko; Fujita, Kazutoshi; Shishikura, Ayako [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Takahara, Taro; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Miyata, Daiki [Kanagawa Children' s Medical Center, Department of Circulation Medicine, Yokohama (Japan); Inoue, Tomio [Yokohama City University, Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2010-10-15

    Microsusceptibility changes in the brain are well known to correspond with microbleeds or micrometal fragments in adults, but this phenomenon has not been explored well in children. To assess imaging and clinical characteristics of children with multiple foci of microsusceptibility changes using susceptibility-weighted imaging (SWI). Between 2006 and 2008, 12 children with multiple foci of microsusceptibility on SWI without corresponding abnormal signal on conventional MRI were identified and were retrospectively assessed. The locations of foci of microsusceptibility included the cerebral white matter, basal ganglia, brainstem and cerebellar white matter, without any clear systematic anatomic distribution. CT (n = 5) showed no calcification at the locations corresponding to the microsusceptibility on SWI. Conventional MR imaging showed white matter volume loss (n = 5), delayed myelination (n = 2), acute infarction (n = 1), chronic infarction (n = 1), meningitis (n = 1), slight signal abnormality in the white matter (n = 1) and no abnormal findings (n = 1). Follow-up SWI (n = 3) showed no change of the microsusceptibility foci. Interestingly, all children had a history of heart surgery under extracorporeal circulation for congenital heart disease. Multiple foci of microsusceptibility can be seen in the brain on SWI in children with congenital heart disease who underwent heart surgery with extracorporeal circulation. (orig.)

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  7. SPECT/spiral-CT hybrid imaging in unclear foci of increased bone metabolism: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Roemer, W.; Kuwert, T. [Nuklearmedizinische Klinik, Friedrich-Alexander-Univ. Erlangen/Nuernberg (Germany); Beckmann, M.W. [Frauenklinik, Friedrich-Alexander-Univ. Erlangen/Nuernberg (Germany); Forst, R. [Lehrstuhl fuer Orthopaedie mit Orthopaedischer Chirurgie, Friedrich-Alexander Univ. Erlangen/Nuernberg (Germany); Bautz, W. [Radiologisches Inst., Friedrich-Alexander-Univ. Erlangen/Nuernberg (Germany)

    2005-07-01

    In bone scintigraphy, the differentiation between degenerative processes and bone metastases is still difficult. Therefore, additional radiological studies are regularly needed after bone scintigraphy. The now introduced hybrid-cameras combining single-photon emission computed tomography (SPECT) and spiral-CT are unique in the sense that they offer the opportunity to correlate the functional information with morphology in one session. We herein present two patients in whom this technological setup allowed a definite diagnosis in scintigraphically unclear vertebral lesions. In a patient with breast cancer, hypermetabolic lesions were clearly correlated with osteolyses. In another patient with synovial carcinoma, spondylosis and spondylarthrosis caused focal tracer uptake in the lumbar spine. In addition to an improved diagnostic accuracy, SPECT/Spiral-CT will considerably abbreviate the diagnostic process. (orig.)

  8. Why should I share my knowledge? A multiple foci of commitment perspective

    DEFF Research Database (Denmark)

    Swart, Juani; Kinnie, Nicholas; van Rossenberg, Yvonne Gerarda Theodora;

    2014-01-01

    Knowledge-intensive firms need to leverage their individual knowledge assets via knowledge sharing to create collective knowledge resources. This process is, however, in the control of the knowledge worker. We explore this personal and emotive quality of knowledge sharing by asking: ‘How does emp...... of the interrelationship between (a) the types and foci of commitment and (b) bidirectional knowledge sharing.......Knowledge-intensive firms need to leverage their individual knowledge assets via knowledge sharing to create collective knowledge resources. This process is, however, in the control of the knowledge worker. We explore this personal and emotive quality of knowledge sharing by asking: ‘How does...

  9. Mechanisms of multiple myeloma bone disease

    Science.gov (United States)

    Galson, Deborah L; Silbermann, Rebecca; Roodman, G David

    2012-01-01

    Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies. PMID:23951515

  10. Fabrication of microscale medical devices by two-photon polymerization with multiple foci via a spatial light modulator.

    Science.gov (United States)

    Gittard, Shaun D; Nguyen, Alexander; Obata, Kotaro; Koroleva, Anastasia; Narayan, Roger J; Chichkov, Boris N

    2011-11-01

    Two-photon polymerization is an appealing technique for producing microscale devices due to its flexibility in producing structures with a wide range of geometries as well as its compatibility with materials suitable for biomedical applications. The greatest limiting factor in widespread use of two-photon polymerization is the slow fabrication times associated with line-by-line, high-resolution structuring. In this study, a recently developed technology was used to produce microstructures by two-photon polymerization with multiple foci, which significantly reduces the production time. Computer generated hologram pattern technology was used to generate multiple laser beams in controlled positions from a single laser. These multiple beams were then used to simultaneously produce multiple microstructures by two-photon polymerization. Arrays of micro-Venus structures, tissue engineering scaffolds, and microneedle arrays were produced by multifocus two-photon polymerization. To our knowledge, this work is the first demonstration of multifocus two-photon polymerization technology for production of a functional medical device. Multibeam fabrication has the potential to greatly improve the efficiency of two-photon polymerization production of microscale devices such as tissue engineering scaffolds and microneedle arrays.

  11. [The new TNM classification for lung tumors : Changes and the assessment of multiple tumor foci].

    Science.gov (United States)

    Harms, A; Kriegsmann, M; Fink, L; Länger, F; Warth, A

    2017-02-01

    Recently a new TNM classification for tumors of the lung was published, encompassing some relevant changes, for example how to deal with multiple lung tumors. This article comprehensively describes respective changes. Furthermore, background information on how the new TNM classification was built and what should be done in the future to further improve prognosis and outcome prediction is reviewed.

  12. Multiple fluid-filled bone metastases.

    Science.gov (United States)

    Frenzel, Laurent; Javier, Rose-Marie; Eichler, Francoise; Zollner, Goerg; Sibilia, Jean

    2010-03-01

    Bone metastases are usually seen on imaging studies as lytic lesions and less often as sclerotic or mixed lesions. We report an exceedingly unusual case of breast cancer identified after magnetic resonance imaging showed bone metastases with fluid-fluid levels in the spine and sacrum. Bone images containing fluid-fluid levels are usually solitary abnormalities produced by aneurismal bone cysts. The fluid-fluid level is due to bleeding within the tumor followed by layering of the blood components based on density differences. Only two other cases of bone metastases with multiple fluid-fluid levels have been reported. Although fluid-fluid levels are exceedingly rare, clinicians should be aware that they might indicate a malignancy, particularly when they are multiple.

  13. Promoting Psychology to Students: Embracing the multiplicity of research foci and method

    Directory of Open Access Journals (Sweden)

    Clare Samantha Rees

    2013-10-01

    Full Text Available In order for the discipline of psychology to continue to thrive it is imperative that future students are effectively recruited into the field. Research is an important part of the discipline and it is argued that the nature of psychological research is naturally one of multiplicity in topic and methodology and that promoting and highlighting this should be considered as a potentially effective recruitment strategy. In this study, a snap-shot of current research topics and methodologies was collected based on published papers from one typical academic psychology department in Australia. Fifty articles published in the period 2010-2013 were randomly selected and then grouped using content analysis to form topic clusters. Five main clusters were identified and included: Grief and Loss; Psychopathology; Sociocultural Studies; Attachment and Parenting; and Developmental Disorders. The studies spanned the full spectrum of research methodologies from quantitative to qualitative and had implications for assessment practices, diagnosis, prevention and treatment, education, and policy. The findings are discussed in terms of the unique characteristics of psychology as a discipline and how this diversity ought to be utilized as the main sell

  14. Enzootic plague foci, Algeria

    Science.gov (United States)

    Malek, M.A.; Hammani, A.; Beneldjouzi, A.; Bitam, I.

    2014-01-01

    In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8%) rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague. PMID:25834736

  15. Enzootic plague foci, Algeria

    Directory of Open Access Journals (Sweden)

    M.A. Malek

    2015-03-01

    Full Text Available In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8% rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague.

  16. Bone Health in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Vit Zikan

    2011-01-01

    Full Text Available Multiple sclerosis (MS is a gait disorder characterized by acute episodes of neurological defects leading to progressive disability. Patients with MS have multiple risk factors for osteoporotic fractures, such as progressive immobilization, long-term glucocorticoids (GCs treatment or vitamin D deficiency. The duration of motor disability appears to be a major contributor to the reduction of bone strength. The long term immobilization causes a marked imbalance between bone formation and resorption with depressed bone formation and a marked disruption of mechanosensory network of tightly connected osteocytes due to increase of osteocyte apoptosis. Patients with higher level of disability have also higher risk of falls that combined with a bone loss increases the frequency of bone fractures. There are currently no recommendations how to best prevent and treat osteoporosis in patients with MS. However, devastating effect of immobilization on the skeleton in patients with MS underscores the importance of adequate mechanical stimuli for maintaining the bone structure and its mechanical competence. The physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, particularly osteocyte apoptosis, will be promising for prevention and treatment of osteoporosis in patients with MS.

  17. Peculiar chondroblastoma involving multiple tarsal bones

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Masaharu [Jikei University School of Medicine, Department of Pathology, Tokyo (Japan); the Jikei University Daisan Hospital, Department of Pathology, Tokyo (Japan); Asanuma, Kazuo [Jikei University School of Medicine, Department of Orthopedic Surgery, Tokyo (Japan); Irie, Takeo [Jikei University School of Medicine, Department of Radiology, Tokyo (Japan)

    2010-07-15

    A case of peculiar chondroblastoma involving multiple tarsal bones in a 49-year-old woman is described. The patient presented with pain and swelling of the right foot. Radiographs revealed a lytic expansile lesion of medial, intermediate, and lateral cuneiform bones, navicular, cuboid, and tarsal bones of the right foot, indicating a malignant tumor. Biopsies demonstrated a diffuse proliferation of round cells with eccentric and indented nuclei with longitudinal grooves and eosinophilic cytoplasm. Atypia was prominent, but mitotic figures were rare. The stroma was chondroid with focal chicken-wire calcification. On electron microscopy, the tumor exhibited chondroblastic features. The patient is alive with the tumor 7 years after radiotherapy. The tumor is considered a chondroblastoma with low malignant potential. (orig.)

  18. Analysis of Lymphocytic DNA Damage in Early Multiple Sclerosis by Automated Gamma-H2AX and 53BP1 Foci Detection: A Case Control Study.

    Directory of Open Access Journals (Sweden)

    Ludwig Rasche

    Full Text Available In response to DNA double-strand breaks, the histone protein H2AX becomes phosphorylated at its C-terminal serine 139 residue, referred to as γ-H2AX. Formation of γ-H2AX foci is associated with recruitment of p53-binding protein 1 (53BP1, a regulator of the cellular response to DNA double-strand breaks. γ-H2AX expression in peripheral blood mononuclear cells (PBMCs was recently proposed as a diagnostic and disease activity marker for multiple sclerosis (MS.To evaluate the significance of γ-H2AX and 53BP1 foci in PBMCs as diagnostic and disease activity markers in patients with clinically isolated syndrome (CIS and early relapsing-remitting MS (RRMS using automated γ-H2AX and 53BP1 foci detection.Immunocytochemistry was performed on freshly isolated PBMCs of patients with CIS/early RRMS (n = 25 and healthy controls (n = 27 with γ-H2AX and 53BP1 specific antibodies. Nuclear γ-H2AX and 53BP1 foci were determined using a fully automated reading system, assessing the numbers of γ-H2AX and 53BP1 foci per total number of cells and the percentage of cells with foci. Patients underwent contrast enhanced 3 Tesla magnetic resonance imaging (MRI and clinical examination including expanded disability status scale (EDSS score. γ-H2AX and 53BP1 were also compared in previously frozen PBMCs of each 10 CIS/early RRMS patients with and without contrast enhancing lesions (CEL and 10 healthy controls.The median (range number of γ-H2AX (0.04 [0-0.5] and 53BP1 (0.005 [0-0.2] foci per cell in freshly isolated PBMCs across all study participants was low and similar to previously reported values of healthy individuals. For both, γ-H2AX and 53BP1, the cellular focus number as well as the percentage of positive cells did not differ between patients with CIS/RRMS and healthy controls. γ-H2AX and 53BP1 levels neither correlated with number nor volume of T2-weighted lesions on MRI, nor with the EDSS. Although γ-H2AX, but not 53BP1, levels were higher in

  19. Multiple Metastasis-Like Bone Lesions in Scintigraphic Imaging

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    2012-01-01

    Full Text Available Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS with technetium-99m methylene diphosphonate (Tc-99m MDP demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG, multiple myeloma (MM, disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases.

  20. Role of osteocytes in multiple myeloma bone disease

    Science.gov (United States)

    Delgado-Calle, Jesus; Bellido, Teresita; Roodman, G. David

    2014-01-01

    Purpose of review Despite the increased knowledge of osteocyte biology, the contribution of this most abundant bone cell to the development and progression of multiple myeloma in bone is practically unexplored. Recent findings Multiple myeloma bone disease is characterized by exacerbated bone resorption and the presence of osteolytic lesions that do not heal because of a concomitant reduction in bone formation. Osteocytes produce molecules that regulate both bone formation and resorption. Recent findings suggest that the life span of osteocytes is compromised in multiple myeloma patients with bone lesions. In addition, multiple myeloma cells affect the transcriptional profile of osteocytes by upregulating the production of pro-osteoclastogenic cytokines, stimulating osteoclast formation and activity. Further, patients with active multiple myeloma have elevated circulating levels of sclerostin, a potent inhibitor of bone formation which is specifically expressed by osteocytes in bone. Summary Understanding the contribution of osteocytes to the mechanisms underlying the skeletal consequences of multiple myeloma bone disease has the potential to provide important new therapeutic strategies that specifically target multiple myeloma–osteocyte interactions. PMID:25289928

  1. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

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

    Science.gov (United States)

    Vilanova, J C; Luna, A

    2016-04-01

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

  3. Reconstruction of multiple metacarpal bone defect using segmentated free fibular bone flap: Case report

    Directory of Open Access Journals (Sweden)

    Rahmi Evinc

    2014-04-01

    Full Text Available In this report we present a case of blast injury to hand, including multiple metacarpal bone defect. Bone defects were reconstructed using fibular flap. Structural integrity of metacarpal bones was preserved with good functional results. [Hand Microsurg 2014; 3(1.000: 29-32

  4. Reconstruction of multiple metacarpal bone defect using segmentated free fibular bone flap: Case report

    OpenAIRE

    Rahmi Evinc; Can Kopal; Dogan Bek; Muzaffer Durmus

    2014-01-01

    In this report we present a case of blast injury to hand, including multiple metacarpal bone defect. Bone defects were reconstructed using fibular flap. Structural integrity of metacarpal bones was preserved with good functional results. [Hand Microsurg 2014; 3(1.000): 29-32

  5. Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, Niels; Brixen, Kim; Eriksen, Erik Fink

    2004-01-01

    BACKGROUND AND OBJECTIVES: Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate...... 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS: Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were...

  6. The Multiple Roles of Microrna-223 in Regulating Bone Metabolism

    Directory of Open Access Journals (Sweden)

    Yong Xie

    2015-10-01

    Full Text Available Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this review, we highlight the roles of miR-223 during the processes of osteoclast and osteoblast differentiation, as well as the potential clinical applications of miR-223 in bone metabolism disorders.

  7. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben;

    2015-01-01

    . Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...... transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling...

  8. Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone

    Science.gov (United States)

    Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

    2011-01-01

    Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

  9. Bone marrow myeloid cells in regulation of multiple myeloma progression.

    Science.gov (United States)

    Herlihy, Sarah E; Lin, Cindy; Nefedova, Yulia

    2017-08-01

    Survival, growth, and response to chemotherapy of cancer cells depends strongly on the interaction of cancer cells with the tumor microenvironment. In multiple myeloma, a cancer of plasma cells that localizes preferentially in the bone marrow, the microenvironment is highly enriched with myeloid cells. The majority of myeloid cells are represented by mature and immature neutrophils. The contribution of the different myeloid cell populations to tumor progression and chemoresistance in multiple myeloma is discussed.

  10. The effects of proteasome inhibitors on bone remodeling in multiple myeloma.

    Science.gov (United States)

    Zangari, Maurizio; Suva, Larry J

    2016-05-01

    Bone disease is a characteristic feature of multiple myeloma, a malignant plasma cell dyscrasia. In patients with multiple myeloma, the normal process of bone remodeling is dysregulated by aberrant bone marrow plasma cells, resulting in increased bone resorption, prevention of new bone formation, and consequent bone destruction. The ubiquitin-proteasome system, which is hyperactive in patients with multiple myeloma, controls the catabolism of several proteins that regulate bone remodeling. Clinical studies have reported that treatment with the first-in-class proteasome inhibitor bortezomib reduces bone resorption and increases bone formation and bone mineral density in patients with multiple myeloma. Since the introduction of bortezomib in 2003, several next-generation proteasome inhibitors have also been used clinically, including carfilzomib, oprozomib, ixazomib, and delanzomib. This review summarizes the available preclinical and clinical evidence regarding the effect of proteasome inhibitors on bone remodeling in multiple myeloma. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  12. Visual and quantitative approach to bone marrow foci of increased glucose uptake on PET/CT in a case of aplastic anaemia

    Energy Technology Data Exchange (ETDEWEB)

    Cicone, F. [Sant' Andrea Hospital, Univ. La Sapienza, Rome (Italy). Nuclear Medicine Dept.; Centre Hospitalier Univ. Vaudois (Switzerland). Nuclear Medicine; Lausanne Univ. (Switzerland); Stalder, M. [Institut Central des Hopitaux Valaisans, Sion (Switzerland). Service of Hematology; Cairoli, A. [Centre Hospitalier Univ. Vaudois (Switzerland). Service of Hematology; Lausanne Univ. (Switzerland); Bischof Delaloye, A.; Prior, J.O. [Centre Hospitalier Univ. Vaudois (Switzerland). Nuclear Medicine; Lausanne Univ. (Switzerland); Geiger, D.

    2010-07-01

    This case report shows the clinical impact of a FDG-PET/CT in the assessment of bone marrow (BM) of a patient with aplastic anemia. The feasibility of a quantitative approach to BM intensities on FDG-PET is also discussed. In the authors' opinion, a deeper understanding of the factors that might independently affect FDG uptake and the definition of normal ranges of BM SUV (standardized uptake value) might help to interpret PET/CT images. Further research is needed to understand the physio-pathological basis of FDG uptake in BM and the potential value of its quantification. The analysis of the bone marrow on PET/CT is an interesting field of research. A PET/CT scan contributed to differential diagnosis in a patient with suspected bone marrow aplasia for guiding bone marrow biopsies.

  13. Bone disease in multiple myeloma: pathophysiology and management.

    Science.gov (United States)

    Hameed, Abdul; Brady, Jennifer J; Dowling, Paul; Clynes, Martin; O'Gorman, Peter

    2014-01-01

    Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.

  14. Foci of Volcanoes

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, I.

    1974-01-01

    One may assume a center of volcanic activities beneath the edifice of an active volcano, which is here called the focus of the volcano. Sometimes it may be a ''magma reservoir''. Its depth may differ with types of magma and change with time. In this paper, foci of volcanoes are discussed from the viewpoints of four items: (1) Geomagnetic changes related with volcanic activities; (2) Crustal deformations related with volcanic activities; (3) Magma transfer through volcanoes; and (4) Subsurface structure of calderas.

  15. Lupus pernio with multiple bone cysts in the fingers.

    Science.gov (United States)

    Nagai, Yayoi; Igarashi, Naoya; Ishikawa, Osamu

    2010-09-01

    A 32-year-old Japanese man presented with a 3-year history of purple reddish, and painful swelling of his fingers along with indurated erythema on his nose and ears. He was diagnosed as having sarcoidosis 8 years prior because of uveitis and bilateral hilar lymphadenopathy. X-rays of the hands revealed multiple cystic lesions in the phalanges. Histological examination of the ear revealed epithelioid cell granulomas in the dermis. Oral prednisolone 20 mg/day improved his finger swelling and pain; however, his finger deformities and erythema remain unchanged. Bone involvement is sometimes seen in sarcoidosis and the hands are the most frequently affected areas. The frequency of bone involvement is higher in lupus pernio in comparison with other types of skin sarcoidosis. Systemic corticosteroids could be the first choice of treatment to relieve the symptoms.

  16. Resting and injury-induced inflamed periosteum contain multiple macrophage subsets that are located at sites of bone growth and regeneration.

    Science.gov (United States)

    Alexander, Kylie Anne; Raggatt, Liza-Jane; Millard, Susan; Batoon, Lena; Chiu-Ku Wu, Andy; Chang, Ming-Kang; Hume, David Arthur; Pettit, Allison Robyn

    2017-01-01

    Better understanding of bone growth and regeneration mechanisms within periosteal tissues will improve understanding of bone physiology and pathology. Macrophage contributions to bone biology and repair have been established but specific investigation of periosteal macrophages has not been undertaken. We used an immunohistochemistry approach to characterize macrophages in growing murine bone and within activated periosteum induced in a mouse model of bone injury. Osteal tissue macrophages (osteomacs) and resident macrophages were distributed throughout resting periosteum. In tissues collected from 4-week-old mice, osteomacs were observed intimately associated with sites of periosteal diaphyseal and metaphyseal bone dynamics associated with normal growth. This included F4/80(+)Mac-2(-/low) osteomac association with extended tracks of bone formation (modeling) on diphyseal periosteal surfaces. Although this recapitulated endosteal osteomac characteristics, there was subtle variance in the morphology and spatial organization of periosteal modeling-associated osteomacs, which likely reflects the greater structural complexity of periosteum. Osteomacs, resident macrophages and inflammatory macrophages (F4/80(+)Mac-2(hi)) were associated with the complex bone dynamics occurring within the periosteum at the metaphyseal corticalization zone. These three macrophage subsets were also present within activated native periosteum after bone injury across a 9-day time course that spanned the inflammatory through remodeling bone healing phases. This included osteomac association with foci of endochondral ossification within the activated native periosteum. These observations confirm that osteomacs are key components of both osteal tissues, in spite of salient differences between endosteal and periosteal structure and that multiple macrophage subsets are involved in periosteal bone dynamics.

  17. Multiple bone metastases seen on radionuclide bone scans and distributed to batson's plexus

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Tae Yong; Lee, Suck Hong; Kim, Byung Soo; Chung, Hyun Woo [Pusan Univ. College of Medicine, Pusan (Korea, Republic of); Huh, Jin Do [Kosin Mecial College, Pusan (Korea, Republic of); Lee, Young Il; Park, Byung Ho [Donga Univ. College of Medicine, Pusan (Korea, Republic of); Lee, Young Joon; Eun, Choong Ki [Inje University. College of Medicine, Pusan (Korea, Republic of)

    1998-08-01

    Multiple bone metastases that appear on 99mTc-MDP bone scans tend to be distributed in the axial skeleton, including the proximal humeri and femora;this is similar to the distribution seen in Batson's paravertebral plexus. The purpose of this study was, therefore, to evaluate- by examining the anatomic distribution of metastases- the metastatic mechanism of cancer cells of various primary tumors in Batson's plexus.Materials and Methods: Three hundred and forth-five known cases of primary tumors and multiple bone metastases were confirmed by bone scan imaging. The axial skeleton was divided into seven parts: skull, ribs, scapulas,spine, pelvis, proximal humeri, and proximal femora. In addition, the spine was divided into cervical, thoracic and lumbar areas. Results: Among the 345 cases, bony metastases were distributed as follows: ribs, 186 (53.9%);spinal areas, 172 (49.9%); pelvis, 94 (27.2%); proximal femora, 85 (24.6%); skull, 63 (18.3%); proximal humeri, 45(13%); and scapulas, 31 (9%). Among the 243 primarily thoracic cancer cases (e.g. lung, breast or esophagus),distribution was as follows: ribs, 142 (58.4%); spinal areas 111 (45.7%); and pelvis, 54 (22.2%). Among the 69 cancers which were primarily of the upper abdomen (e.g. stomach or liver), distribution spinal areas, 44 (63.8%);ribs, 33 (47.8%); and pelvis, 26 (37.7%). While the 33 primarily pelvic cancers (e.g. prostate, uterine cervix or bladder), were distributed between spinal areas (17, 51.5%), the pelvis (13, 39.4%), and the ribs (11, 33.3%).There were no statistically significant differences in the distribution of bony metastases according to primary cancers. Conclusion: Multiple bone metastases, as seen on bone scan images, coincided with the distribution of Batson's plexus. We therefore conclude that although pelvic tumors can metastasize to the axial skeleton by directly anatomising into Batson's plexus, other primary tumors metastasize from systemic veins to Batson

  18. Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

    Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  19. Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

    Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  20. Factors Affecting Bone Mineral Density in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Azin Ayatollahi

    2013-01-01

    Full Text Available Background: Multiple sclerosis (MS is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD.Methods: 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA. The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS. The patient’s quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29.Results: Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001, but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL, disease duration and BMD of both site.Conclusion: As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients

  1. Multiple verification in computational modeling of bone pathologies

    CERN Document Server

    Liò, Pietro; Paoletti, Nicola; 10.4204/EPTCS.67.8

    2011-01-01

    We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the...

  2. Bone morphogenetic proteins in multiple sclerosis: Role in neuroinflammation.

    Science.gov (United States)

    Eixarch, Herena; Calvo-Barreiro, Laura; Montalban, Xavier; Espejo, Carmen

    2017-02-27

    Bone morphogenetic proteins (BMPs) are growth factors that represent the largest subgroup of signalling ligands of the transforming growth factor beta (TGF-β) superfamily. Their participation in the proliferation, survival and cell fate of several cell types and their involvement in many pathological conditions are now well known. BMP expression is altered in multiple sclerosis (MS) patients, suggesting that BMPs have a role in the pathogenesis of this disease. MS is a demyelinating and neurodegenerative autoimmune disorder of the central nervous system (CNS). MS is a complex pathological condition in which genetic, epigenetic and environmental factors converge, although its aetiology remains elusive. Multifunctional molecules, such as BMPs, are extremely interesting in the field of MS because they are involved in the regulation of several adult tissues, including the CNS and the immune system. In this review, we discuss the extensive data available regarding the role of BMP signalling in neuronal progenitor/stem cell fate and focus on the participation and expression of BMPs in CNS demyelination. Additionally, we provide an overview of the involvement of BMPs as modulators of the immune system, as this subject has not been thoroughly explored even though it is of great interest in autoimmune disorders. Moreover, we describe the data on BMP signalling in autoimmunity and inflammatory diseases, including MS and its experimental models. Thus, we aim to provide an integrated view of the putative role of BMPs in MS pathogenesis and to open the field for the further development of alternative therapeutic strategies for MS patients.

  3. Value of bone scan in the McCune-Albright syndrome. Report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Edeburn, G.F.; Mortensson, W.

    Bone scintigraphy proved valuable in diagnosing McCune-Albright's syndrome in a 6-year-old girl by detecting multiple, non-symptomatic foci in the skull, axial skeleton and in the extremities. Subsequent roentgen examination showed abnormal bone structure in the affected areas, consistent with fibrous dysplasia.

  4. Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, Niels; Brixen, Kim; Eriksen, Erik Fink

    2004-01-01

    -terminal (PINP) propeptides of procollagen I, bone-specific alkaline phosphatase, and osteocalcin were measured to estimate bone formation. Dual energy X-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD) of the lumbar spine, hip, and whole body. Serum and urine samples were collected every...

  5. SERUM YKL-40 IS ASSOCIATED WITH BONE DISEASE IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Abildgaard, Niels; Johansen, Julia S.

    2007-01-01

     Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix...... to progression of myeloma-related bone disease. A potential role for YKL-40 in the bone disease of MM must be considered....

  6. [Evaluation of multiple myeloma with bone scintigraphy using Tc 99 diphosphonate. Review of the literature].

    Science.gov (United States)

    Solis, O J; Gonzales, R; De Luca, S; McKusick, K A; Potsaid, M S

    1977-04-01

    Bone Scanning using 99m Tc-Diphosphonate is another diagnostic modality in the evaluation of multiple mieloma which allows the identification of bone lesions not demonstrable by conventional radiography. The use of 99m Tc-Diphosphonate is more convenient and less harmful than other radioactive isotopes utilized before.

  7. Polymorphisms in the heparanase gene in multiple myeloma association with bone morbidity and survival

    DEFF Research Database (Denmark)

    Andersen, Niels F; Vogel, Ulla; Klausen, Tobias W;

    2015-01-01

    described, and some are associated with haematological malignancies. METHODS: In this study, we evaluated four SNPs rs11099592, rs4364254, rs4693608 and rs6535455 in the HSPE gene in 348 newly diagnosed multiple myeloma patients with focus on bone morbidity (lytic bone disease and vertebral fractures...

  8. Intrauterine dwarfism, peculiar facies and thin bones with multiple fractures - a new syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Kan, A.

    1988-07-01

    Three newborns with thin ribs and thin long bones with multiple fractures are reported. Whereas one patient presents a syndromic association of bone dysplasia and intrauterine dwarfism two other patients cannot be appropriately evaluated due to lack of basic clinical and pathologic data.

  9. A Case Report of Multiple Aneurysmal Bone Cysts

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Case Report A 30-year old male patient, admitted in our hospital for a fracture of the upper end of the left humerus in February, 2006, received treatment with curettage of the lesion in combination with an autologous bone graft from the right ilium plus internal fixation. A post-operative pathological examination indicated that there was a simple bone cyst in the area of the fracture, with a satisfactory postoperative recovery.

  10. Diagnosis and Treatment of Bone Disease in Multiple Myeloma: Spotlight on Spinal Involvement

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2013-01-01

    Full Text Available Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation of vertebral alterations, as it allows to detect not only the exact morphology of the lesions, but also the pattern of bone marrow infiltration by the disease. Multiple treatment modalities can be used to manage multiple myeloma-related vertebral lesions. Surgery or radiotherapy is mainly employed in case of spinal cord compression, impending fractures, or intractable pain. Percutaneous vertebroplasty or balloon kyphoplasty can reduce local pain in a significant fraction of treated patients, without interfering with subsequent therapeutic programs. Systemic antimyeloma therapy with conventional chemotherapy or, more appropriately, with combinations of conventional chemotherapy and compounds acting on both neoplastic plasma cells and bone marrow microenvironment must be soon initiated in order to reduce bone resorption and, possibly, promote bone formation. Bisphosphonates should also be used in combination with antimyeloma therapy as they reduce bone resorption and prolong patients survival. A multidisciplinary approach is thus needed in order to properly manage spinal involvement in multiple myeloma.

  11. Half body irradiation of patients with multiple bone metastases: A phase II trial

    DEFF Research Database (Denmark)

    Berg, Randi; Yilmaz, Mette; Høyer, Morten

    2009-01-01

    AIM OF STUDY: The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. PATIENTS AND METHODS: A total of 44 patients received...... on the patients' global quality of life. CONCLUSION: Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases....

  12. Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease

    DEFF Research Database (Denmark)

    Kristensen, Ida B; Christensen, Jacob H; Lyng, Maria Bibi

    2013-01-01

    Lytic bone disease (LBD) in multiple myeloma (MM) is caused by osteoclast hyperactivation and osteoblast inhibition. Based on in vitro studies, the hepatocyte growth factor (HGF) pathway is thought to be central in osteoblast inhibition. We evaluated the gene expression of the HGF pathway in vivo...

  13. {sup 18}F-FDG PET/CT bone/bone marrow findings in Hodgkin's lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging

    Energy Technology Data Exchange (ETDEWEB)

    Moulin-Romsee, Gerard [Universite Paris 7, Service de Medicine Nucleaire, Hopital Saint-Louis, Assistance Publique-Hopitaux de Paris (France); Institut Curie, Nuclear Medicine, Paris (France); Hindie, Elif; Filmont, Jean-Emmanuel; Moretti, Jean-Luc [Universite Paris 7, Service de Medicine Nucleaire, Hopital Saint-Louis, Assistance Publique-Hopitaux de Paris (France); Cuenca, Xavier; Brice, Pauline; Sibon, David [Hopital Saint-Louis, Haemato-Oncology, Paris (France); Decaudin, Didier; Anitei, Marcela [Institut Curie, Haematology, Paris (France); Benamor, Myriam [Institut Curie, Nuclear Medicine, Paris (France); Briere, Josette [Hopital Saint-Louis, Pathology, Paris (France); Kerviler, Eric de [Hopital Saint-Louis, Radiology, Paris (France)

    2010-06-15

    Accurate staging of Hodgkin's lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. {sup 18}F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant {sup 18}F-FDG PET/CT. Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and {sup 18}F-FDG PET/CT. Results of BMB were not available at the time of {sup 18}F-FDG PET/CT imaging. Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on {sup 18}F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on {sup 18}F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy {sup 18}F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient. {sup 18}F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging. (orig.)

  14. Segmentation of multiple knee bones from CT for orthopedic knee surgery planning.

    Science.gov (United States)

    Wu, Dijia; Sofka, Michal; Birkbeck, Neil; Zhou, S Kevin

    2014-01-01

    Patient-specific orthopedic knee surgery planning requires precisely segmenting from 3D CT images multiple knee bones, namely femur, tibia, fibula, and patella, around the knee joint with severe pathologies. In this work, we propose a fully automated, highly precise, and computationally efficient segmentation approach for multiple bones. First, each bone is initially segmented using a model-based marginal space learning framework for pose estimation followed by non-rigid boundary deformation. To recover shape details, we then refine the bone segmentation using graph cut that incorporates the shape priors derived from the initial segmentation. Finally we remove overlap between neighboring bones using multi-layer graph partition. In experiments, we achieve simultaneous segmentation of femur, tibia, patella, and fibula with an overall accuracy of less than 1mm surface-to-surface error in less than 90s on hundreds of 3D CT scans with pathological knee joints.

  15. A case of multiple bone fractures due to the use of topical corticosteroid therapy for psoriasis.

    Science.gov (United States)

    Gönül, Müzeyyen; Gönül, Engin

    2015-06-01

    A 45-year-old man who had psoriasis had applied topical clobetasol 17 propionate ointment on his whole body 2-3 times a week after the bath for 20 years. Physical examination showed abdominal distension, atrophy all over the skin, psoriatic plaques on the trunk, and extremities and multiple striae on the shoulders and legs. Morning plasma cortisol level and ACTH stimulation test confirmed the diagnosis of hypothalamic insufficiency. Bone mineral densitometry showed severe osteoporosis. Multiple bone fractures in the vertebrae and costa were detected on lumbar magnetic resonance imaging, the (99)Tc MDP whole-body bone scan, and thoracoabdominal computerized tomography imaging. Topical corticosteroid therapies have possible local and/or systemic side effects such as atrophy, telangiectasia, hypertricosis, and suppression of pituitary-adrenal axis. We present an interesting case with multiple bone fractures caused by long-time topical corticosteroid use.

  16. Bone loss and fractures in multiple sclerosis: focus on epidemiologic and physiopathological features

    Directory of Open Access Journals (Sweden)

    Dionyssiotis Y

    2011-07-01

    Full Text Available Yannis DionyssiotisRehabilitation Department, Physical and Social Rehabilitation Center, Amyntæo, Florina, GreeceAbstract: Multiple sclerosis (MS affects the central nervous system leading to disability and is complicated by bone loss and fractures. Despite the acceptance of osteoporosis and fractures as two major public health problems, in people with MS the mechanisms have not been investigated adequately. Physicians and patients usually focus on the major cause of disability and neglect the multiple risk factors for osteoporosis and fractures in this specific population. This review updates the epidemiology and physiopathological mechanisms in MS.Keywords: multiple sclerosis, bone, fractures, osteoporosis, osteopenia

  17. Bone And Soft Tissue Changes In Patients With Spinal Cord Injury And Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dionyssiotis Yannis

    2014-12-01

    Full Text Available In patients with spinal cord injury and multiple sclerosis, deterioration of body composition (changes in bone, fat and muscle mass is associated with increased risk for diseases such as coronary artery heart disease, non-insulin dependent diabetes mellitus, lipid metabolism abnormalities, and osteoporotic fractures in these patients. Immobility leads to a changing pattern of loading in the paralyzed areas, and secondary alteration in structure. However, bone and soft tissue changes in these patients are usually neglected. The purpose of this article is to update on the pathophysiological mechanisms leading to bone and soft tissue changes, and to increase the awareness of the treating physicians with respect to bone, muscle and fat loss and their consequences aiming to obtain measures to prevent bone and soft tissue loss in these patients.

  18. Upregulation of Syndecan-1 in the bone marrow microenvironment in multiple myeloma is associated with angiogenesis

    DEFF Research Database (Denmark)

    Andersen, Niels F; Kristensen, Ida B; Preiss, Birgitte S

    2014-01-01

    OBJECTIVES: Syndecan-1 (SDC1), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL6) are expressed by malignant plasma cells and cells in the bone marrow microenvironment and may be involved in the angiogenic process in multiple myeloma (MM). METHODS...... expression of HGF, VEGF and IL6 was seen. CONCLUSION: Our study indicates that SDC1 expressed by the bone marrow microenvironment is involved in angiogenesis in MM....

  19. Archival Bone Marrow Samples: Suitable for Multiple Biomarker Analysis?

    DEFF Research Database (Denmark)

    Lund, Bendik; Najmi, A. Laeya; Wesolowska, Agata

    2015-01-01

    Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole...... biopsies from 18 Danish and Norwegian childhood acute lymphoblastic leukemia patients were included and compared with corresponding blood samples. Samples were grouped according to the age of sample and whether WGA was performed or not. We found that measurements of DNA concentration after DNA extraction...

  20. An unusual case of hypercortisolism with multiple weight-bearing bone fractures.

    Science.gov (United States)

    Papadakis, Georgios; Uebelhart, Brigitte; Goumaz, Michel; Zawadynski, Sophie; Rizzoli, Rene

    2013-09-01

    Glucocorticoid excess, either from exogenous exposure or through endogenous overproduction, is a common cause of secondary osteoporosis. We report a 52-year-old woman presenting with multiple stress fractures of the lower extremities, despite various osteoporosis therapeutic regimens. Investigations led to the diagnosis of hypercortisolism of pituitary origin. Pituitary surgery was unsuccessful, justifying a treatment of ketoconazole. In the absence of densitometric osteoporosis, assessment of bone microstructure using high resolution peripheral quantitative computed tomography revealed alterations of both the cortical and trabecular compartments. This case illustrates that hypercortisolism may cause bone fragility in the absence of marked changes in areal bone mineral density.

  1. Independent scattering model and velocity dispersion in trabecular bone: comparison with a multiple scattering model.

    Science.gov (United States)

    Haïat, G; Naili, S

    2011-02-01

    Speed of sound measurements are used clinically to assess bone strength. Trabecular bone is an attenuating composite material in which negative values of velocity dispersion have been measured; this behavior remaining poorly explained physically. The aim of this work is to describe the ultrasonic propagation in trabecular bone modeled by infinite cylinders immersed in a saturating matrix and to derive the physical determinants of velocity dispersion. An original homogenization model accounting for the coupling of independent scattering and absorption phenomena allows the computation of phase velocity and of dispersion while varying bone properties. The first step of the model consists in the computation of the attenuation coefficient at all frequencies. The second step of the model corresponds to the application of the general Kramers-Krönig relationship to derive the frequency dependence of phase velocity. The model predicts negative values of velocity dispersion in agreement with experimental results obtained in phantoms mimicking trabecular bone. In trabecular bone, only negative values of velocity dispersion are predicted by the model, which span within the range of values measured experimentally. However, the comparison of the present results with results obtained in Haiat et al. (J Acoust Soc Am 124:4047-4058, 2008) assuming multiple scattering indicates that accounting for multiple scattering phenomena leads to a better prediction of velocity dispersion in trabecular bone.

  2. Diagnosing osteomyelitis: evaluation and significance of multiple tracer bone imaging

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, W.B.; Graebner, J.E.; Arenson, D.J.

    The use of various radioactive compounds in the diagnosis of osteomyelitis has been the topic of discussion by numerous authors. A great number of bone imaging agents have been experimented with and clinically applied with varying results. It is the intention of this article to detail and compare the use of two such agents: technetium-99m phosphonate, a phosphorus compound radioactively labeled with an isotope of technetium, and gallium citrate 67, a radioactive isotope of gallium. Both of these materials have specific indications and limitations. However, used in the proper setting, either singularly or in conjunction, they give the clinician precise information about pathologic processes. It is the clinician's careful interpretation of both positive and negative test results that enables him to make proper diagnosis and thus institute appropriate therapy.

  3. N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Mylin, Anne K; Gøtze, Jens P.; Heickendorff, Lene;

    2015-01-01

    AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were ev...

  4. Bone marrow lambda-type light chain crystalline structures associated with multiple myeloma.

    Science.gov (United States)

    Schvartz, H; Bonhomme, P; Caulet, S; Beorchia, A; Patey, M; Caulet, T

    1985-01-01

    A 58-year-old man showed bone marrow crystalline structures associated with a lambda light chain producing multiple myeloma. Analysis and processing of electron images clearly displayed the periodic structure of the crystals. Immunochemistry suggested that they contained the whole or a fragmented constant portion of immunoglobulin.

  5. Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease

    Science.gov (United States)

    D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J.; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L.; Patrene, Kenneth D.; Yu, Shibing; Velu, Chinavenmeni S.; Xiao, Guozhi; Grimes, H. Leighton; Roodman, G. David

    2011-01-01

    Protracted inhibition of osteoblast (OB) differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. However, the underlying pathophysiology for this prolonged OB suppression is unknown. Therefore, we developed a mouse MM model in which the bone marrow stromal cells (BMSCs) remained unresponsive to OB differentiation signals after removal of MM cells. We found that BMSCs from both MM-bearing mice and MM patients had increased levels of the transcriptional repressor Gfi1 compared with controls and that Gfi1 was a novel transcriptional repressor of the critical OB transcription factor Runx2. Trichostatin-A blocked the effects of Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter. MM-BMSC cell-cell contact was not required for MM cells to increase Gfi1 and repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1 induction was blocked by anti–TNF-α and anti–IL-7 antibodies. Importantly, BMSCs isolated from Gfi1−/− mice were significantly resistant to MM-induced OB suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MM patients significantly restored expression of Runx2 and OB differentiation markers. Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression and provide a new therapeutic target for MM bone disease. PMID:22042697

  6. A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

    Science.gov (United States)

    Noonan, Kimberly; Marchionni, Luigi; Anderson, Judy; Pardoll, Drew; Roodman, G. David

    2010-01-01

    Osteoclast (OC)–mediated lytic bone disease remains a cause of major morbidity in multiple myeloma. Here we demonstrate the critical role of interleukin-17–producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an interleukin-17 phenotype that enhances OC activation. In univariate analyses of factors mediating bone destruction, levels of cytokines that selectively induce and maintain the Th17 phenotype tightly correlated with the extent of bone disease in myeloma. In contrast, MILs activated under conditions that skew toward a Th1 phenotype significantly reduced formation of mature OC. These findings demonstrate that interleukin-17 T cells are critical to the genesis of myeloma bone disease and that immunologic manipulations shifting MILs from a Th17 to a Th1 phenotype may profoundly diminish lytic bone lesions in multiple myeloma. PMID:20664052

  7. Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics.

    Science.gov (United States)

    Garcia-Gomez, Antonio; Sanchez-Guijo, Fermin; Del Cañizo, M Consuelo; San Miguel, Jesus F; Garayoa, Mercedes

    2014-07-26

    Multiple myeloma is a hematological malignancy in which clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic lesions due to increased osteoclast (OC) activity and suppressed osteoblast (OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells (MSCs) play a critical role in multiple myeloma pathophysiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of myeloma bone disease (MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients (pMSCs) and their healthy counterparts (dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibitory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and activity at various levels (i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncoupling ephrinB2-EphB4 signaling, and through augmented production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents (at preclinical or clinical stage) targeting those signaling pathways is commented.

  8. Consideration of multiple load cases is critical in modelling orthotropic bone adaptation in the femur.

    Science.gov (United States)

    Geraldes, Diogo M; Modenese, Luca; Phillips, Andrew T M

    2016-10-01

    Functional adaptation of the femur has been investigated in several studies by embedding bone remodelling algorithms in finite element (FE) models, with simplifications often made to the representation of bone's material symmetry and mechanical environment. An orthotropic strain-driven adaptation algorithm is proposed in order to predict the femur's volumetric material property distribution and directionality of its internal structures within a continuum. The algorithm was applied to a FE model of the femur, with muscles, ligaments and joints included explicitly. Multiple load cases representing distinct frames of two activities of daily living (walking and stair climbing) were considered. It is hypothesised that low shear moduli occur in areas of bone that are simply loaded and high shear moduli in areas subjected to complex loading conditions. In addition, it is investigated whether material properties of different femoral regions are stimulated by different activities. The loading and boundary conditions were considered to provide a physiological mechanical environment. The resulting volumetric material property distribution and directionalities agreed with ex vivo imaging data for the whole femur. Regions where non-orthogonal trabecular crossing has been documented coincided with higher values of predicted shear moduli. The topological influence of the different activities modelled was analysed. The influence of stair climbing on the properties of the femoral neck region is highlighted. It is recommended that multiple load cases should be considered when modelling bone adaptation. The orthotropic model of the complete femur is released with this study.

  9. Half body irradiation of patients with multiple bone metastases: A phase II trial

    DEFF Research Database (Denmark)

    Berg, Randi; Yilmaz, Mette; Høyer, Morten

    2009-01-01

    AIM OF STUDY: The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. PATIENTS AND METHODS: A total of 44 patients received...... on the patients' global quality of life. CONCLUSION: Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases....... lower (n = 37), upper (n = 5), or sequential HBI (n = 2). The dose for lower HBI was 8 Gy in one fraction and for upper HBI 7 Gy in one fraction, with reduction of the lung dose to 6 Gy in one fraction by partial shielding. The majority of patients (n = 41) were males with prostate cancers (93...

  10. Multiple Low Energy Long Bone Fractures in the Setting of Rothmund-Thomson Syndrome

    Directory of Open Access Journals (Sweden)

    Nicholas Beckmann

    2015-01-01

    Full Text Available Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy as well as various skeletal anomalies, juvenile cataracts, and predisposition to certain cancers. Although Rothmund-Thomson syndrome is associated with diminished bone mineral density in addition to multiple skeletal abnormalities, there are few reports of the association with stress fractures or pathologic fractures in low energy trauma or delayed healing of fractures. Presented is a case of a young adult male with Rothmund-Thomson syndrome presenting with multiple episodes of long bone fractures caused by low energy trauma with one of the fractures exhibiting significantly delayed healing. The patient was also found to have an asymptomatic stress fracture of the lower extremity, another finding of Rothmund-Thomson syndrome rarely reported in the literature. A thorough review of the literature and comprehensive presentation of Rothmund-Thomson syndrome is provided in conjunction with our case.

  11. Controlled multiple growth factor delivery from bone tissue engineering scaffolds via designed affinity.

    Science.gov (United States)

    Suárez-González, Darilis; Lee, Jae Sung; Diggs, Alisha; Lu, Yan; Nemke, Brett; Markel, Mark; Hollister, Scott J; Murphy, William L

    2014-08-01

    It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release. We hypothesized that mineral coatings could be used as a platform for controlled incorporation and release of multiple growth factors. Specifically, mineral-coated scaffolds were "dip coated" in multiple growth factor solutions, and growth factor binding and release were dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate (β-TCP) scaffolds were fabricated using indirect solid-free form fabrication techniques and coated with a thin conformal mineral layer. Mineral-coated β-TCP scaffolds were sequentially dipped in recombinant human vascular endothelial growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral-binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for the incorporation of each growth factor. The dual release profile showed sustained release of both growth factors for over more than 60 days. Scaffolds releasing either rhVEGF alone or the combination of growth factors showed an increase in blood vessel ingrowth in a dose-dependent manner in a sheep intramuscular implantation model. This approach demonstrates a "modular design" approach, in which a controllable biologics carrier is integrated into a structural scaffold as a thin surface coating.

  12. Bone marrow microenvironment-derived signals induce Mcl-1 dependence in multiple myeloma.

    Science.gov (United States)

    Gupta, Vikas A; Matulis, Shannon M; Conage-Pough, Jason E; Nooka, Ajay K; Kaufman, Jonathan L; Lonial, Sagar; Boise, Lawrence H

    2017-04-06

    Multiple myeloma is highly dependent on the bone marrow microenvironment until progressing to very advanced extramedullary stages of the disease such as plasma cell leukemia. Stromal cells in the bone marrow secrete a variety of cytokines that promote plasma cell survival by regulating antiapoptotic members of the Bcl-2 family including Mcl-1, Bcl-xL, and Bcl-2. Although the antiapoptotic protein on which a cell depends is typically consistent among normal cells of a particular phenotype, Bcl-2 family dependence is highly heterogeneous in multiple myeloma. Although normal plasma cells and most multiple myeloma cells require Mcl-1 for survival, a subset of myeloma is codependent on Bcl-2 and/or Bcl-xL We investigated the role of the bone marrow microenvironment in determining Bcl-2 family dependence in multiple myeloma. We used the Bcl-2/Bcl-xL inhibitor ABT-737 to study the factors regulating whether myeloma is Mcl-1 dependent, and thus resistant to ABT-737-induced apoptosis, or Bcl-2/Bcl-xL codependent, and thus sensitive to ABT-737. We demonstrate that bone marrow stroma is capable of inducing Mcl-1 dependence through the production of the plasma cell survival cytokine interleukin-6 (IL-6). IL-6 upregulates Mcl-1 transcription in a STAT3-dependent manner, although this occurred in a minority of the cells tested. In all cells, IL-6 treatment results in posttranslational modification of the proapoptotic protein Bim. Phosphorylation of Bim shifts its binding from Bcl-2 and Bcl-xL to Mcl-1, an effect reversed by MEK inhibition. Blocking IL-6 or downstream signaling restored Bcl-2/Bcl-xL dependence and may therefore represent a clinically useful strategy to enhance the activity of Bcl-2 inhibitors. © 2017 by The American Society of Hematology.

  13. Pelvic Gliomatosis within Foci of Endometriosis

    OpenAIRE

    Killeen, Vincent B.; Reich, Harry; McGlynn, Fran; Virgilio, Lawrence A.; Krawitz, Michael A.; Sekel, Lisa

    1997-01-01

    The third reported case of pelvic gliomatosis found within foci of endometriosis is documented 16 years after the removal of a benign cystic teratoma. Grossly at laparoscopy the lesions appear as typical deep fibrotic endometriotic implants.

  14. Bone marrow uptake of {sup 99m}Tc-MIBI in patients with multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Fonti, R. [Medicina Nucleare, Facolta di Medicina, Univ. Federico II, Naples (Italy); Centro per la Medicina Nucleare C.N.R., Cattedra di Medicina Nucleare, Napoli (Italy); Del Vecchio, S.; Zannetti, A.; Di Gennaro, F.; Pace, L.; Salvatore, M. [Centro per la Medicina Nucleare C.N.R., Cattedra di Medicina Nucleare, Napoli (Italy); De Renzo, A.; Catalano, L.; Califano, C.; Rotoli, B. [Cattedra di Ematologia, Dipt. di Medicina Clinica e Sperimentale, Napoli (Italy)

    2001-02-01

    In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile ({sup 99m}Tc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively {sup 99m}Tc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with {sup 99m}Tc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent {sup 99m}Tc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of {sup 99m}Tc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of {sup 99m}Tc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of {sup 99m}Tc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner

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

    Science.gov (United States)

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

    2007-12-01

    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.

  16. Locating Ectopic Foci on a Cylinder

    Science.gov (United States)

    Kuklik, Pawel; Zebrowski, Jan J.

    2003-07-01

    Arrhythmia is a condition in which an additional ectopic pacemaker is present in the tissue of the heart. Localization of ectopic foci is essential for successful radio-frequency ablation, an important surgical way of treating arrhythmia. In one of the possible mechanisms, arrhythmia induced by an ectopic foci located in one of the main blood vessels leading out or onto the heart. The therapeutic procedure in this case is usually ablation of the whole junction of the blood vessel with heart wall. In this way, whatever excitation occurs inside the vessel, it cannot penetrate the ventricles perturbing their contraction cycle. Such an ablation procedure is long and burdened with the risk of the perforation. A more safe method would involve the localization of the source of the excitation (i.e. the ectopic foci) and its ablation. The methods used in cardiology at present involve complicated localization systems and are time-consuming with the patient spending a long time on the operating table. Recently, Hall and Glass have developed numerical methods which allow to quickly to model the localization of the ectopic foci in a flat, square sample of an inhomogeneous medium. Here, we demonstrate an extension of this model for the case of a cylinder containing an ectopic foci, that can be a model of a blood vessel with the source of the ectopic beat inside it. Three methods of localization are implemented. Standard electrodes containing several active tips are used to stimulate the medium locally and locate the foci judging from the reaction of the system. The first one uses electrode activation times to compute the location of the ectopic site. The second one localizes it by measuring the resetting response of the foci, and the third one, uses wavefront curvature. Specifically for the cylindrical geometry of the blood vessel, we developed a localization procedure that allows to quickly localize the pacemaker.

  17. Familial multiple exostosis arising from bones of enchondral as well as membranous (in a family affecting seven members

    Directory of Open Access Journals (Sweden)

    Maruti Kambali

    2012-01-01

    Full Text Available Familial multiple exostosis in a family of seven members who are affected found that exostosis was arising both from bones of enchondral as well as membranous ossification, which was sessile as well as pedunculated and was larger in size at the growing ends of the bones. The lesions occur only in bones that develop from cartilage (endochondral ossification. In our study, we have noticed lesions occurring in both endochondral as well as membranous bone. Till now, no article has mentioned about membranous origin (clavicle.

  18. International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

    Science.gov (United States)

    Terpos, Evangelos; Morgan, Gareth; Dimopoulos, Meletios A.; Drake, Matthew T.; Lentzsch, Suzanne; Raje, Noopur; Sezer, Orhan; García-Sanz, Ramón; Shimizu, Kazuyuki; Turesson, Ingemar; Reiman, Tony; Jurczyszyn, Artur; Merlini, Giampaolo; Spencer, Andrew; Leleu, Xavier; Cavo, Michele; Munshi, Nikhil; Rajkumar, S. Vincent; Durie, Brian G.M.; Roodman, G. David

    2013-01-01

    Purpose The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease. Methodology An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Recommendations Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability. PMID:23690408

  19. Maintaining bone health in patients with multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Miceli, Teresa S; Colson, Kathleen; Faiman, Beth M; Miller, Kena; Tariman, Joseph D

    2011-08-01

    About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice.

  20. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  1. Doença óssea em Mieloma Múltiplo Bone disease in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Vania T. M. Hungria

    2007-03-01

    Full Text Available As principais manifestações clínicas do mieloma múltiplo estão relacionadas à destruição óssea. Esta doença óssea pode levar a fraturas patológicas, compressão da medula espinhal, hipercalcemia e dor, sendo uma das principais causas de morbidade e mortalidade. Estas complicações resultam do desequilíbrio da reabsorção e formação óssea, decorrente do aumento da atividade osteoclástica. Este aumento é mediado pela liberação de fatores ativadores dos osteoclastos, que são produzidos no microambiente da medula óssea por células tumorais e não tumorais. Os bisfosfonatos são inibidores específicos da atividade osteoclástica e são eficazes no tratamento da hipercalcemia associada às neoplasias malignas e podem reduzir o aparecimento de complicações esqueléticas. Estudos recentes identificaram novas moléculas como o receptor de ativação nuclear kappa B (RANK, seu ligante (RANKL, osteoprotegerina (OPG, e a proteína inflamatória dos macrófagos-1alfa, que estão envolvidas na ativação e diferenciação dos osteoclastos, enquanto que a proteína dikkopf-1 inibe a formação óssea osteoblástica. Estas novas moléculas parecem não só interferir na biologia da destruição óssea do mieloma, mas também com a sobrevida e crescimento tumoral, sendo novos alvos para o desenvolvimento de drogas antimieloma. Estudos recentes com anticorpo monoclonal anti-RANKL são promissores. O tratamento da doença óssea do mieloma múltiplo inclui principalmente o uso de bisfosfonatos, radioterapia e procedimentos cirúrgicos.The major clinical manifestation of multiple myeloma is related to osteolytic bone destruction. Bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain, and is a major cause of morbidity and mortality. These complications result from asynchronous bone turnover wherein increased osteoclastic bone resorption is not accompanied by a comparable increase in bone formation

  2. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    Science.gov (United States)

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  3. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients.

    Directory of Open Access Journals (Sweden)

    Liesbeth Bieghs

    Full Text Available Insulin-like growth factor (IGF signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM. In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6, leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17, monoclonal gammopathy of undetermined significance (MGUS (n = 37, and control individuals (n = 15, using ELISA (IGFs and 125I-IGF1 Western Ligand Blotting (IGFBPs. MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5-3.8 fold and decrease in intact IGFBP-3 (0.6-0.5 fold in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration.

  4. Local radiotherapy for palliation in multiple myeloma patients with symptomatic bone lesions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Won; Lee, Jeong Eun [Dept. of Radiation Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2016-03-15

    To evaluate the clinical outcomes of symptomatic bone lesions in patients with multiple myeloma (MM) who received local radiotherapy (LRT). Fifty-one patients with 87 symptomatic bone lesions treated via LRT were analyzed. LRT was delivered at a median total dose of 21 Gy (range, 12 to 40 Gy) in a median of 7 fractions (range, 4 to 20 fractions). The clinical outcomes of LRT and the factors affecting treatment response were assessed. After a median follow-up time of 66.7 weeks, symptom relief was achieved for 85 of 87 lesions (97.7%). The median time to symptom relief was 7 days from the start of LRT (range, 1 to 67 days). The duration of in-field failure-free survival ranged from 1.1 to 450.9 weeks (median, 66.7 weeks). The radiation dose or use of previous and concurrent chemotherapy was not significantly associated with in-field failure for LRT (p = 0.354, 0.758, and 0.758, respectively). Symptomatic bone lesions in patients with MM can be successfully treated with LRT. A higher radiation dose or the use of concurrent chemotherapy may not influence the in-field disease control. A relatively low radiation dose could achieve remission of symptoms in patients with MM.

  5. [Monitoring the natural foci of tularemia on Wrangel Island].

    Science.gov (United States)

    Podobedova, Ia S; Meshcheriakova, I S; Demidova, T N; Kormilitsyna, M I; Mikhaĭlova, T V; Baraniuk, V V

    2013-01-01

    Long-term annual monitoring of the natural foci of tularemia was first made on Wrangel Island. The objects of the investigation were pellets of birds-myophages, blood samples from rodents, and excrements from carnivorous mammals. A total of 2626 biological samples were examined in the period 2002 to 2011. A serological test was ascertained to be the most effective method for the detection of tularemia epizooties; polymerase chain reaction should be used as an additional technique to examine blood samples, as well as rodent tubular bone debris taken from the pellets. Tularemia epizooties were registered in the populations of two species of lemmings every year, except in 2003. An intensive diffuse tularemia epizooty was first detected in this area, which emerged in 2019, peaked by spring 2011, and covered most of the island. The antigen of tularemia pathogen was identified in 43.46% of the samples under examination,which is a high quantitative indicator of the intensity of an epizootic process. The fact that positive samples are annually found in the same areas of the island suggests that the causative agent is steadily and long preserved in the parasitic system. The availability of stable and active natural tularemia foci on Wrangel Island calls for preventive measures, particularly vaccination of risk groups coming to the island to conduct researches.

  6. Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice

    National Research Council Canada - National Science Library

    Xin Zhou; Zhaoping Zhang; Jian Q. Feng; Vladmir M. Dusevich; Krishna Sinha; Hua Zhang; Bryant G. Darnay; Benoit de Crombrugghe; Eric N. Olson

    2010-01-01

    The transcription factor Osterix (Osx) is required for osteoblast differentiation and bone formation during embryonic development, but it is not known whether Osx has an essential function in postnatal bone growth and in bone homeostasis...

  7. High serum YKL-40 concentration is associated with severe bone disease in newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Mylin, Anne Kærsgaard; Abildgaard, N.; Johansen, J.S.

    2008-01-01

    Objectives: In multiple myeloma (MM) YKL-40 is present in the bone marrow microenvironment and is suggested to play a role in remodelling of the extracellular matrix. Here, the association between serum YKL-40 and severity of bone disease in MM is investigated. Methods: Serum YKL-40 was measured...... in 34 MM patients at diagnosis. Bone disease was assessed by radiography and biochemical markers of bone metabolism. Patients were treated with conventional chemotherapy and followed for up to 30 months. Results: Patients with a serum YKL-40 elevated above the age specific reference range (56%) had...... a higher total X-ray score (P = 0.003) and higher levels of the markers of bone resorption serum C-terminal telopeptide of collagen type I (P = 0.003), urine pyridinoline (P = 0.04) and urine deoxypyridinoline (P = 0.002), while the levels of urine N-terminal telopeptide of collagen type I (NTX-1...

  8. Bidirectional Notch signaling and osteocyte-derived factors in the bone marrow microenvironment promote tumor cell proliferation and bone destruction in multiple myeloma

    Science.gov (United States)

    Delgado-Calle, Jesus; Anderson, Judith; Cregor, Meloney D.; Hiasa, Masahiro; Chirgwin, John M.; Carlesso, Nadia; Yoneda, Toshiyuki; Mohammad, Khalid S.; Plotkin, Lilian I.; Roodman, G. David; Bellido, Teresita

    2016-01-01

    In multiple myeloma (MM) increased numbers of monoclonal plasma cells in the bone marrow induce localized osteolytic lesions that rarely heal, due to increased bone resorption and suppressed bone formation. Numerous studies reported the contributions that different cell types in the MM microenvironment make to MM growth and bone disease, but the role of matrix-embedded osteocytes in MM, which comprise >95% of bone cells and are major regulators of osteoclast and osteoblast activity, is unclear. We report that osteocytes in MM-bearing bones physically interact with MM cells in vivo, undergo caspase3-dependent apoptosis, and express higher RANKL and Sclerostin levels than osteocytes from control mice. Mechanistic studies revealed that osteocyte apoptosis is initiated by activation of Notch signaling in osteocytes through direct contact with MM cells, and is further amplified by MM cell-secreted TNFα. This Notch/TNFα induced osteocyte apoptosis increases osteocytic Rankl expression, the osteocytic Rankl/Opg ratio and the ability of osteocytes to attract osteoclast precursors to induce local bone resorption. Further, osteocytes in contact with MM cells express high levels of Sost/Sclerostin that decrease Wnt signaling in osteoblasts and inhibit osteoblast differentiation. Importantly, direct contact between osteocytes and MM cells reciprocally activates Notch signaling and increases Notch receptor expression in MM cells, in particular Notch3 and 4, and stimulates MM cell growth. These studies reveal a previously unknown role for bidirectional Notch signaling between MM cells and osteocytes that enhances MM growth and bone disease, and suggest the potential of targeting osteocyte-MM cell interactions as a novel MM treatment. PMID:26833121

  9. Investigation on natural radionucildes levels in multiple media in bone-coal mine areas of five provinces

    Institute of Scientific and Technical Information of China (English)

    KONG Ling-Li; ZHANG Liang; LI Ying; YE Ji-Da; JIANG Shan; SHI Jin-Hua; WU Zong-Mei

    2005-01-01

    This paper reports methods and results of the investigation of natural radionuclides levels in multiple media in the bone-coal mine areas in Hubei, Hunan, Jiangxi, Zhejiang, and Anhui Provinces. In the studied bone-coal mine areas, the specific activities of 238U and 226Ra in the soil samples were 0.37 and 0.24 Bq/g, respectively; the specific activities of 226Ra in the samples of bone-coal, bone-coal cinder and bone-coal cinder brick (BCCB) were 1.3,1.4 and 0.9 Bq/g, respectively. In the water samples collected from the bone-coal mine areas, the average concentrations of natural uranium and 226Ra were 33μg/L and 58 mBq/L, respectively, while in the water samples collected from outside the bone-coal mine areas, they were 3.4μg/L and 45 mBq/L, respectively. In addition, the specific activities of 238U and 226Ra in air aerosol samples from the bone-coal mine areas were 0.6 and 0.5 mBq/m3, respectively.

  10. Role of Immunotherapy in Targeting the Bone Marrow Microenvironment in Multiple Myeloma: An Evolving Therapeutic Strategy.

    Science.gov (United States)

    Chung, Clement

    2017-01-01

    Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor. Accordingly, a need exists for new therapeutic avenues that can overcome resistance to current therapies and improve survival outcomes. In addition, myeloma is associated with progressive immune dysregulation, with defects in T-cell immunity, natural killer cell function, and the antigen-presenting capacity of dendritic cells, resulting in a tumor microenvironment that promotes disease tolerance and progression. Together, the immunosuppressive microenvironment and oncogenic mutations activate signaling networks that promote myeloma cell survival. Immunotherapy incorporates novel treatment options (e.g., monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapy, immune checkpoint inhibitors, bispecific antibodies, and tumor vaccines) either alone or in combination with existing lines of therapies (e.g., immunomodulatory agents, proteasome inhibitors, and histone deacetylase inhibitors) to enhance the host anti myeloma immunity within the bone marrow microenvironment and improve clinical response. Following the U.S. Food and Drug Administration approval of daratumumab and elotuzumab in 2015, more immunotherapeutic agents are expected to be become available as valuable treatment options in the near future. This review provides a basic understanding of the role of immunotherapy in modulating the bone marrow tumor microenvironment and its role in the treatment of myeloma. Clinical efficacy and safety of recently

  11. Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells.

    Science.gov (United States)

    Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R

    2016-01-01

    In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT.

  12. Dissecting the Multiple Myeloma-bone microenvironment reveals new therapeutic opportunities

    Science.gov (United States)

    Shay, G; Hazlehurst, L; Lynch, CC

    2015-01-01

    Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease. PMID:26423531

  13. Implications of combined ovariectomy/multi-deficiency diet on rat bone with age-related variation in bone parameters and bone loss at multiple skeletal sites by DEXA.

    Science.gov (United States)

    Govindarajan, Parameswari; Schlewitz, Gudrun; Schliefke, Nathalie; Weisweiler, David; Alt, Volker; Thormann, Ulrich; Lips, Katrin Susanne; Wenisch, Sabine; Langheinrich, Alexander C; Zahner, Daniel; Hemdan, Nasr Y; Böcker, Wolfgang; Schnettler, Reinhard; Heiss, Christian

    2013-02-28

    Osteoporosis is a multi-factorial, chronic, skeletal disease highly prevalent in post-menopausal women and is influenced by hormonal and dietary factors. Because animal models are imperative for disease diagnostics, the present study establishes and evaluates enhanced osteoporosis obtained through combined ovariectomy and deficient diet by DEXA (dual-energy X-ray absorptiometry) for a prolonged time period. Sprague-Dawley rats were randomly divided into sham (laparotomized) and OVX-diet (ovariectomized and fed with deficient diet) groups. Different skeletal sites were scanned by DEXA at the following time points: M0 (baseline), M12 (12 months post-surgery), and M14 (14 months post-surgery). Parameters analyzed included BMD (bone mineral density), BMC (bone mineral content), bone area, and fat (%). Regression analysis was performed to determine the interrelationships between BMC, BMD, and bone area from M0 to M14. BMD and BMC were significantly lower in OVX-diet rats at M12 and M14 compared to sham rats. The Z-scores were below -5 in OVX-diet rats at M12, but still decreased at M14 in OVX-diet rats. Bone area and percent fat were significantly lower in OVX-diet rats at M14 compared to sham rats. The regression coefficients for BMD vs. bone area, BMC vs. bone area, and BMC vs. BMD of OVX-diet rats increased with time. This is explained by differential percent change in BMD, BMC, and bone area with respect to time and disease progression. Combined ovariectomy and deficient diet in rats caused significant reduction of BMD, BMC, and bone area, with nearly 40% bone loss after 14 months, indicating the development of severe osteoporosis. An increasing regression coefficient of BMD vs. bone area with disease progression emphasizes bone area as an important parameter, along with BMD and BMC, for prediction of fracture risk.

  14. Half body irradiation of patients with multiple bone metastases: A phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Berg, Randi S.; Yilmaz, Mette K. (Dept. of Oncology, Aalborg Hospital, Aarhus Univ., Aalborg (Denmark)); Hoeyer, Morten; Nielsen, Ole S. (Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)); Keldsen, Nina (Dept. of Oncology, Herning Hospital, Herning (Denmark)); Ewertz, Marianne (Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark))

    2009-05-15

    Aim of study. The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. Patients and methods. A total of 44 patients received lower (n = 37), upper (n = 5), or sequential HBI (n = 2). The dose for lower HBI was 8 Gy in one fraction and for upper HBI 7 Gy in one fraction, with reduction of the lung dose to 6 Gy in one fraction by partial shielding. The majority of patients (n = 41) were males with prostate cancers (93%). Outcome and side effects were measured by the EORTC Quality of Life Questionnaire C30 (QLQ-C30), and by the doctors' toxicity scores in the medical record. Pain relief was defined as a reduction of more than 10 points on the QLQ-C30 scale. Evaluations were performed before and 2, 4, 8, 16, and 24 weeks after treatment. Results. Relief of pain was observed in 76% of the patients receiving HBI with 8.8% of the patients experiencing complete pain relief with no residual pain in the treated field. For most patients, the pain relief was lasting throughout the follow-up period. About one third of the patients were able to reduce their intake of analgesics. Grade 1-2 diarrhoea was the most common side effect observed in 49% of the patients two weeks after treatment. Mild pulmonary symptoms (grade 1-2) were observed in four of seven patients receiving upper HBI. No clear effect was observed on the patients' global quality of life.Conclusion. Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases.

  15. Bone x-ray

    Science.gov (United States)

    ... or broken bone Bone tumors Degenerative bone conditions Osteomyelitis (inflammation of the bone caused by an infection) ... Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Osteomyelitis Paget disease of the bone Rickets X-ray ...

  16. Actin Foci Adhesion of D. discoideum

    Science.gov (United States)

    Flanders, Bret; Paneru, Govind

    2014-03-01

    Amoeboid migration is a fast (10 μm min-1) integrin-independent mode of migration that is important with D. discoideum, leukocytes, and breast cancer cells. It is poorly understood, but depends on the establishment of adhesive contacts to the substrate where the cell transmits traction forces. In pre-aggregative D. discoideum, a model system for learning about amoeboid migration, these adhesive contacts are discrete complexes that are known as actin-foci. They have an area of ~ 0.5 μm2 and a lifetime of ~ 20 s. This talk will present measurements of the adhesive character of actin foci that have been obtained using a submicron force transducer that was designed for this purpose. Results on the rupture stresses and lifetimes of individual acting foci under nano-newton level forces will be described in the context of a general theory for cellular adhesion. This theory depends on, essentially, three cellular properties: the membrane-medium surface tension, the number density of adhesion receptors in the membrane, and the receptor-substrate potential energy surface. Therefore, the use of the transducer to determine the surface tension will be presented, as well.

  17. Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: a retrospective study of 418 cases of carcinomas.

    Science.gov (United States)

    Boros, Monica; Marian, Cristina; Moldovan, Cosmin; Stolnicu, Simona

    2012-10-15

    The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated. A retrospective study of 418 cases of breast carcinomas was conducted over a 3-year period. The histological tumor types and histological grades of multifocal/multicentric carcinomas in each tumor focus were compared, and mismatches among foci were recorded. Ninety-one of the 418 cases reviewed had multiple carcinomas (21.77%). A comparison between multiple synchronous tumor foci revealed that their histological type was different in 12.08% of the cases. Mismatches among foci were also observed in 9.89% of the cases when evaluating the histological grade, and 5 out of 9 additional tumor foci with a different grade from the largest (index) tumor (55.55%) displayed a higher grade compared to the index tumor. Since the histological tumor type and histological grade of the individual foci may vary considerably within the same tumor and the additional foci may be of higher grade than the index tumor, we believe that reporting morphologic parameters with more unfavorable characteristics in addition to the parameters of the index tumor is imperative.

  18. Detection of Unknown sites of multiple enchondroma (Ollier′s Disease mimicking like metastasis using bone scintigraphy

    Directory of Open Access Journals (Sweden)

    Koramadai Karuppusamy Kamaleshwaran

    2015-01-01

    Full Text Available Ollier′s disease characterized by multiple skeletal enchondroma is a rare noninherited disease of unknown etiology. Majority of the skeletal enchondroma are present in the metaphyses and diaphysis of tubular limb bones. Ollier′s disease has a predilection for unilateral distribution. Malignant changes in Ollier′s disease may occur in adult patients. Radionuclide bone scanning is one method used to assess lesions depicted on radiographs or magnetic resonance images that are presumed to be enchondromas. Furthermore, a bone scan may give a clue to the multifocality of the disease. We report a case of right first phalangeal enchondroma in a 23-year-old male, who underwent bone scintigraphy detected multifocal asymmetric right side involvement of radius, humerus, femur, and tibia which confirm a diagnosis of Ollier′s disease.

  19. 18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Cassou-Mounat, Thibaut [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France); Balogova, Sona [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Nataf, Valerie [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Radiopharmacy, Hopital Tenon, Paris (France); Calzada, Marie [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Huchet, Virginie; Kerrou, Khaldoun [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Devaux, Jean-Yves [AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France); Mohty, Mohamad; Garderet, Laurent [Universite Pierre et Marie Curie (UPMC), Paris (France); INSERM, UMRS 938, Proliferation and Differentiation of Stem Cells, Paris (France); AP-HP, Departement d' Hematologie et de Therapie Cellulaire, Hopital Saint Antoine, Paris (France); Talbot, Jean-Noel [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France)

    2016-10-15

    Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG. (orig.)

  20. SERUM YKL-40 IS ASSOCIATED WITH BONE DISEASE IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Abildgaard, Niels; Johansen, Julia S.

    2007-01-01

    , in angiogenesis, and in cancer cell survival and invasion. The aim of this study was to investigate the association between serum YKL-40 (S-YKL-40) and the degree of bone disease in MM. Materials and Methods. S-YKL-40 was measured using an ELISA in 54 MM patients at diagnosis. Bone morbidity was assessed...... to progression of myeloma-related bone disease. A potential role for YKL-40 in the bone disease of MM must be considered....

  1. The multiple myeloma bone eco-system and its relation to oncogenesis.

    Science.gov (United States)

    Bataille, R

    2015-06-01

    Pure lytic bone lesions are the hallmark of myeloma (MM). MM is the only hematological malignancy associated with lytic bone lesions and the mechanisms of bone destruction are well documented both at the cellular and molecular levels. An uncoupling bone process characterizes MM, with stimulation of bone resorption and inhibition of bone formation. The capacity of MM cells to directly or indirectly inhibit bone formation is specific of MM, although many carcinomas have the capacity to stimulate bone resorption, directly or indirectly in a similar way to MM. Few MM do not develop bone lesions, while true sclerotic MM remain exceptional. Inhibition of bone formation is the major event explaining the transition from MGUS to overt MM. It is now well documented that bone cells regulate MM cell growth, osteoclast stimulating MM cell growth and osteoblasts inhibiting it. Progression of MM from MGUS is characterized by the selection of MM clones able to inhibit osteoblasts, favoring tumor growth. These data underline the interest of new treatments able to regenerate bone.

  2. Optimally enhanced heating for focused ultrasound surgery with split foci, dual-frequency, or multi foci

    Science.gov (United States)

    Lu, Mingzhu; Guan, Yubo; Dong, Tengju; Liu, Fenfen; Wan, Mingxi

    2017-03-01

    To substantially enhance heating in HIFU treatment, several methods such as split foci, multi foci, and dual-frequency modes are used. The enhanced-cavitation heating protocols are implemented experimentally in BSA gel-phantom using four-element split-focus array. Using dual frequency of 1.2 and 2.4 MHz, the superimposing of two frequency pressures at confocal region can enhance nucleation cavitation and inertial cavitation activity. When using 135° phase shift combined with dual frequency of 1.2 and 2.4 MHz, the peak negative pressure reach maximum due to peak-negative pressures of two frequencies occur at same time, resulting strong cavitation activities. When using dual frequency of 1.2 and 2.4 MHz, 25-Hz pulse-repetition frequency (PRF), both 135° and 180° phase shift protocols, the experiment results show the largest lesion size of 10.5 × 10.5 × 11 mm3, quickest lesion inception time of less than 0.2 s, therefore, both 135° and 180° phase shift protocols are most efficient in enhanced-cavitation heating. The filtered-PCD mean square waveforms reveal that the strong inertial-cavitation activities involve in those two treatments. The lesion size of four foci of 180° phase shift, single frequency, 25 Hz PRF, is 2 times that of 0° phase shift, single frequency even if the peak intensity of 180° case is half less than that of 0° phase shift case. When arrange multi foci using phased array in a style of a wavelength distance between neighbor foci in focal plane, the result is the same as that using split foci of 180° phase shift and single frequency.

  3. Multiple myeloma: Changes in serum C-terminal telopeptide of collagen type I and bone-specific alkaline phosphatase can be used in daily practice to detect imminent osteolysis

    DEFF Research Database (Denmark)

    Lund, Thomas; Abildgaard, Niels; Andersen, Thomas L;

    2010-01-01

    Abstract Objective: Monitoring of bone disease in multiple myeloma is becoming increasingly important since bone protecting treatment with bisphosphonate is becoming restricted after the awareness of osteonecrosis of the jaw. Despite the potential of biochemical markers of bone remodeling...

  4. IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci

    Directory of Open Access Journals (Sweden)

    Lee Eunyoung

    2012-01-01

    Full Text Available Abstract Background Murine experimental autoimmune encephalomyelitis (EAE, a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. Methods We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO and vice versa (IFNγRperiKO. Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Results Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1

  5. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, N; Glerup, H; Rungby, Jørgen

    2000-01-01

    factor (TNF) alpha, TNFbeta, and transforming growth factor (TGF) beta in marrow plasma aspirated from the biopsy area. MARKERS OF BONE RESORPTION: The N-terminal telopeptide of collagen I (Ntx) in urine showed a strong positive correlation with the dynamic histomorphometric indices of bone resorption (r...... with the histomorphometric findings. MARKERS OF BONE FORMATION: Serum C-terminal propeptide of procollagen I (PICP) and serum bone-specific alkaline phosphatase (bAP) showed significant correlations with the dynamic parameters of bone formation (r=0.57-0.58), whereas serum osteocalcin and serum total AP did not. CYTOKINES...... that measurements of the biochemical markers of bone metabolism may be useful in monitoring myeloma bone disease, and might thus be of use for dose titration of bisphosphonate therapy....

  6. Rare presentation of pediatric acute promyelocytic leukemia as multiple lytic bone lesions: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Manjusha Nair

    2014-01-01

    Full Text Available Acute promyelocytic leukemia (APL is an uncommon malignancy in the pediatric population, accounting for only 5-10% of pediatric acute myeloid leukemias, and for this disease to present with bone lesions at diagnosis is extremely unusual. We wish to convey that very rarely, in a pediatric cancer patient presenting with multiple extensive lytic bone lesions, the diagnosis can be APL. The treatment protocol and prognostic implications are vastly different. Histopathology is the gold standard in arriving at a correct diagnosis and delivering proper treatment in such cases. This patient had excellent response to chemotherapy.

  7. In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2

    Science.gov (United States)

    Maes, Ken; Nemeth, Elizabeta; Roodman, G. David; Huston, Alissa; Esteve, Flavia; Freytes, Cesar; Callander, Natalie; Katodritou, Eirini; Tussing-Humphreys, Lisa; Rivera, Seth; Vanderkerken, Karin; Lichtenstein, Alan

    2010-01-01

    Hepcidin is the principal iron-regulatory hormone and a pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. We showed that MM patients had increased serum hepcidin, which inversely correlated with hemoglobin, suggesting that hepcidin contributes to MM-related anemia. Searching for hepcidin-inducing cytokines in MM, we quantified the stimulation of hepcidin promoter-luciferase activity in HuH7 cells by MM sera. MM sera activated the hepcidin promoter significantly more than did normal sera. We then examined the role of bone morphogenetic proteins (BMPs) and interleukin-6 (IL-6), the major transcriptional regulators of hepcidin. Mutations in both BMP-responsive elements abrogated the activation dramatically, while mutations in the IL-6–responsive signal transducer and activator of transcription 3-binding site (STAT3-BS) had only a minor effect. Cotreatment with anti–BMP-2/4 or noggin-Fc blocked the promoter induction with all MM sera, anti–IL-6 blocked it with a minority of sera, whereas anti–BMP-4, -6, or -9 antibodies had no effect. BMP-2–immunodepleted MM sera had decreased promoter stimulatory capacity, and BMP-2 concentrations in MM sera were significantly higher than in normal sera. Our results demonstrate that BMP-2 is a major mediator of the hepcidin stimulatory activity of MM sera. PMID:20679527

  8. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

    Directory of Open Access Journals (Sweden)

    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  9. Diagnostic role of whole body bone scintigraphy in atypical skeletal tuberculosis resembling multiple metastases: a case report

    Directory of Open Access Journals (Sweden)

    Assadi Majid

    2009-11-01

    Full Text Available Abstract Introduction Osseous tuberculosis can be present with unifocal or multifocal bony involvement. Although multifocal involvement of the skeletal system in areas where tuberculosis is endemic is not a rare presentation, its exact prevalence is not well known. A case of atypical skeletal tuberculosis mimicking multiple secondary metastases on radiologic and scintigraphic imaging is presented to emphasize the contribution of bone scintigraphy in the assessment of osseous tuberculosis in typical and atypical presentations. Case presentation A 73-year-old cachectic Asian man (Iranian presented with a general feeling of being unwell and an acute loss of vision in his left eye accompanied by a severe headache. A Tc-99 m-methylene diphosphonate bone scan demonstrated multiple regions of intense activity in the appendicular and axial skeleton, suggesting metastatic involvement. Tumor markers (PSA, CA125, CA 19-9 and AFP were within normal ranges. Based on clinical presentation and laboratory, radiological and scintigraphic findings, a presumptive diagnosis of tuberculosis was made. Quadruple antituberculous chemotherapy was consequently started and the patient later showed marked improvement. Conclusion Scintigraphic bone scanning should be kept in mind when assessing bone pain in patients at a high risk of tuberculosis infection or reactivation. We present this unusual case of multifocal skeletal tuberculosis, and stress the related clinical and diagnostic points with the aim of stimulating a high index of suspicion that could facilitate early diagnosis and appropriate treatment.

  10. PMEL EcoFOCI Early Arctic Data, 1986-1991

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Early Arctic Data, 1987 - 1991

  11. PMEL EcoFOCI Shelikof Line 8 Data, 1981-open

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Shelikof Line 8 Data

  12. Unique effects of energy versus estrogen deficiency on multiple components of bone strength in exercising women.

    Science.gov (United States)

    Southmayd, E A; Mallinson, R J; Williams, N I; Mallinson, D J; De Souza, M J

    2017-04-01

    Many female athletes are energy and/or estrogen deficient, but the independent effects on bone health have not been isolated. Energy deficiency was detrimental at the tibia while estrogen deficiency was detrimental at the radius. Nutrition must be considered alongside menstrual recovery when addressing compromised bone health in female athletes.

  13. Analysis of Bone Mineral Density in Multiple Myeloma: A Comparison of Bone Mineral Density with Plain Radiography, Magnetic Resonance Imaging, and Clinical Staging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Na; Kwon, Soon Tae; Song, Ik Chan [Dept. of Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2013-01-15

    To analyze the bone mineral density (BMD) in multiple myeloma (MM) and to compare BMD with plain radiography, MRI and clinical stage. We reviewed 59 patients with MM and an age- and sex-matched control group, with measured BMD. The L-spine and femoral neck (FN) BMD were measured by dual-energy X-ray absorptiometry. Lateral plain radiographs of the L-spine were graded as 3 stages using the modified Saville index. Four bone marrow patterns were classified on sagittal T1- and T2-weighted magnetic resonance images of the L-spine. BMD in the MM and control group were analyzed. BMD in MM was compared with the modified Saville index, bone marrow patterns on MRI, and clinical stages. In MM, spine BMD was reduced and the difference between spine and FN BMD was larger than the control group (p < 0.001). The modified Saville index was negatively correlated with spine T scores (p < 0.01). The spine BMD in normal marrow pattern on the MRI was the most reduced. There was no statistical correlation between BMD and clinical stage. In MM, spine BMD was significantly reduced and the difference between spine and FN BMD was larger than the control group. The modified Saville index was significantly correlated with spine BMD in MM.

  14. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    DEFF Research Database (Denmark)

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H;

    2013-01-01

    -specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six...

  15. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  16. Bone marrow megakaryocytes, soluble P-selectin and thrombopoietic cytokines in multiple myeloma patients.

    Science.gov (United States)

    Lemancewicz, Dorota; Bolkun, Lukasz; Mantur, Maria; Semeniuk, Janusz; Kloczko, Janusz; Dzieciol, Janusz

    2014-01-01

    The expression of adhesion molecules and other cell-surface molecules is substantial in the communication between plasma cells and bone marrow microenvironment, and may lead to increased proliferation of myeloma cells. Many of the cytokines involved in multiple myeloma (MM) pathogenesis, e.g. thrombopoietin (TPO) and interleukin-6 (IL-6), play a pivotal role in different developmental stages of megakaryocytopoiesis and thrombopoiesis. The principal aim of our study was to explore the relationship between thrombopoietic cytokines, megakaryocytes (MKs) and soluble P-selectin (sP-selectin) levels in MM patients before and after anti-angiogenic treatment. Forty-four patients (20 female and 24 male) with a newly diagnosed MM were examined in three groups, following a division based on the International Staging System, ISS. Plasma levels of TPO, IL-6 and soluble P-selectin (human sP-selectin) were measured by means of ELISA. Bone marrow specimens were studied to determine the number of MKs and the so-called "naked nuclei" (NN), as well as the expression of platelet-derived growth factor (PDGF). The comparison revealed a significantly higher concentration of cytokines and sP-selectin in newly diagnosed MM patients compared to healthy volunteers: for TPO, p=0.01, IL-6, p=0.0005 and sP-selectin, p=0.00008, respectively. Marked differences were observed in the concentration of sP-selectin, expression of PDGF and MKs counts between patients with MM stage I and MM stage III. Statistically meaningful correspondences were also found between MKs versus TPO, NN versus TPO, as well as MKs versus MPV, p=0.009, p=0.004 and p=0.0005, respectively. Furthermore, the analysis exhibited some statistically meaningful divergences between initial concentrations of sP-selectin in subgroups with different response after chemotherapy. The initial concentration of sP-selectin in the group of MM patients with complete or partial remission stood at 31.86 ± 6.13 ng/ml. In the remaining patients

  17. Visualisation of γH2AX foci caused by heavy ion particle traversal; distinction between core track versus non-track damage.

    Directory of Open Access Journals (Sweden)

    Nakako Izumi Nakajima

    Full Text Available Heavy particle irradiation produces complex DNA double strand breaks (DSBs which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle.

  18. Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage

    Science.gov (United States)

    Nakajima, Nakako Izumi; Brunton, Holly; Watanabe, Ritsuko; Shrikhande, Amruta; Hirayama, Ryoichi; Matsufuji, Naruhiro; Fujimori, Akira; Murakami, Takeshi; Okayasu, Ryuichi; Jeggo, Penny; Shibata, Atsushi

    2013-01-01

    Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm) ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci) represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle. PMID:23967070

  19. Samarium-153 EDTMP reduces multiple bone metastasis besides pain relieve; Reduction des metastases osseuses apres traitement au samarium 153-EDTMP en complement de son effet antalgique

    Energy Technology Data Exchange (ETDEWEB)

    Haffaf, E.M.; Oufriha, N. [Hopital Central de l' Armee, Service de Medecine Nucleaire, Alger (Algeria)

    2006-10-15

    This case report shows an almost disappearance of multiple painful bone metastases, on a {sup 99m}Tc-HMDP bone scintigraphy, about three months after administration of {sup 153}Sm-EDTMP (Quadramet in a 78 year-old man with hormone refractory prostate adenocarcinoma. One {sup 153}Sm-EDTMP reduced the PSA level in this patient by more than 70% for at least 2 months. It raises the possibility that this radiopharmaceutical could have therapeutic effect on bone metastasis in addition to its bone pain palliation effect. (authors)

  20. FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis.

    Directory of Open Access Journals (Sweden)

    Alex D Herbert

    Full Text Available Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ.

  1. Additional Detection of Multiple Osteomas in a Patient with Gardner's Syndrome by Bone SPECT/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Hyoung; Kim, Daeweung; Kim, Chang Guhn; Kim, Myoung Hyoun [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

    2013-12-15

    Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which generally develops numerous polyps in the colon and rectum during the second decade of life. Gardner's syndrome is a variant of FAP which has multiple osteomas, dental abnormalities, and fibromas, with incidence ranging between 1 in 4,000 and 1 in 40,000, depending on the region. We present the case of a 35-year-old man referred to our department for bone scintigraphy who was shown to have multiple colon polyps and nuchal type fibroma. In this patient, planar image showed intensely increased uptakes of bone agent in the maxilla and mandible, which are typical findings of Gardner's syndrome. Single photon emission computed tomography/computed tomography (SPECT/CT) was acquired to accurately identify and locate abnormal uptakes detected on planar images. SPECT/CT showed numerous osteomas in the maxilla and mandible where intense uptakes of bone agent were seen. Mildly asymmetrical, focally increased uptake in the superomedial aspect of the left orbit on anterior planar image was shown to be a fontal sinus osteoma on SPECT/CT. Enhanced sensitivity of detecting lesions of SPECT/CT superior to planar scintigraphy has been reported in previous studies. In this report, additional osteomas of sphenoidal and ethmoidal sinuses, which were not seen on planar scintigraphy, were detected by SPECT/CT. This case emphasizes that nuclear physicians should be aware of the typical findings of bone scintigraphy for Gardner's syndrome and also that SPECT/CT could be helpful to diagnose additional lesions not seen on planar images.

  2. Liposome-mediated Functional Expression of Multiple Drug Resistance Gene in Human Bone Marrow CD34+ Cells

    Institute of Scientific and Technical Information of China (English)

    曹文静; 邹萍

    2004-01-01

    Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34 + cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+ cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.01). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34 + cells.

  3. Detection of demineralization in rat legs using multiple-angle x-ray bone densitometry

    Science.gov (United States)

    Jordan, Lawrence M.; DiBianca, Frank A.; Sebes, Jeno I.; Thomason, Donald B.; Zeman, Herbert D.; Davis, Peter G.; Kambeyanda, Dona; Li, Gao; Lovhoiden, Gunnar

    1994-05-01

    A method utilizing digital dual-energy subtraction X-ray radiography for measuring calcium densities localized to the cortical and cancellous regions of bone cross sections is described. The method is being used to study calcium loss in femurs of two differently treated groups of rats. In each experimental cohort, one group of rats is restrained from weightbearing on hind limbs by suspension from a tail harness. The other (control) group is allowed normal weightbearing on all limbs. The densitometry data for each rat leg consists of six X-ray projection images acquired at roughly equal angles about the bone axis by an intensifying screen/CCD camera imaging system. Images of bone cross sections are reconstructed by application of a maximum entropy algorithm constrained by the six projection images. The observed density data are further discriminated into cortical, cancellous and external regions on the basis of reference levels found on image density histograms.

  4. Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

    Science.gov (United States)

    Garcia-Gomez, Antonio; Las Rivas, Javier De; Ocio, Enrique M.; Díaz-Rodríguez, Elena; Montero, Juan C.; Martín, Montserrat; Blanco, Juan F.; Sanchez-Guijo, Fermín M.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

    2014-01-01

    Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease. PMID:25268740

  5. Dentigenous infectious foci – a risk factor of infective endocarditis

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

  6. Fluorescent foci quantitation for high-throughput analysis

    Science.gov (United States)

    Ledesma-Fernández, Elena; Thorpe, Peter H.

    2015-01-01

    A number of cellular proteins localize to discrete foci within cells, for example DNA repair proteins, microtubule organizing centers, P bodies or kinetochores. It is often possible to measure the fluorescence emission from tagged proteins within these foci as a surrogate for the concentration of that specific protein. We wished to develop tools that would allow quantitation of fluorescence foci intensities in high-throughput studies. As proof of principle we have examined the kinetochore, a large multi-subunit complex that is critical for the accurate segregation of chromosomes during cell division. Kinetochore perturbations lead to aneuploidy, which is a hallmark of cancer cells. Hence, understanding kinetochore homeostasis and regulation are important for a global understanding of cell division and genome integrity. The 16 budding yeast kinetochores colocalize within the nucleus to form a single focus. Here we have created a set of freely-available tools to allow high-throughput quantitation of kinetochore foci fluorescence. We use this ‘FociQuant’ tool to compare methods of kinetochore quantitation and we show proof of principle that FociQuant can be used to identify changes in kinetochore protein levels in a mutant that affects kinetochore function. This analysis can be applied to any protein that forms discrete foci in cells. PMID:26290880

  7. Mapping risk foci for endemic sheep scab.

    Science.gov (United States)

    Rose, H; Learmount, J; Taylor, M; Wall, R

    2009-10-28

    Psoroptic mange in sheep, resulting from infestation by the astigmatid mite Psoroptes ovis, is increasingly prevalent in Europe and other parts of the world. As a step towards improved national control, regional or local scab management programmes that target high-risk areas and aim to maintain the number of outbreaks below an acceptable level may be an effective initial use of time and resource. To facilitate such a management approach, in this paper scab outbreak farms are identified using a questionnaire survey of sheep farmers, the data from which are then used to build a national scab risk model for Great Britain. The questionnaire results indicate a national prevalence of scab, between March 2007 and February 2008, of 8.6% (+/-1.98). However, previous exposure to sheep scab significantly affected the respondent's probability of reporting a scab outbreak during the survey period (chi(2)=53.2, d.f.=1, P<0.001); 85% of the farms that reported at least one scab outbreak had experienced outbreaks in previous years, 27% had experienced outbreaks in more than five of the previous 10 years. In contrast, 76% of farms that did not report scab had not had a previous outbreak. The highest prevalence areas were in Northern England, Wales, Southwest England and Scotland. Modelling the distribution of the reported scab outbreaks identified height above sea level, temperature and rainfall as significant predictors of the probability of an outbreak, superimposed on an underlying pattern of sheep abundance. It is argued that scab management programmes directed at these foci have the potential to allow a more targeted approach to scab control and significantly reduce the prevalence of scab in the UK and other European countries.

  8. Expression of osteoblast and osteoclast regulatory genes in the bone marrow microenvironment in multiple myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida B; Christensen, Jacob Haaber; Lyng, Maria Bibi

    2014-01-01

    of osteoclast regulators (RANK, RANKL, OPG, TRAIL, MIP1A), Wnt inhibitors (DKK1, SFRP2, SFRP3, sclerostin, WIF1) and osteoblast transcription factors (RUNX2, osterix) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the bone marrow (BM) microenvironment using snap-frozen BM biopsies...

  9. Single fraction versus multiple fraction radiotherapy for palliation of painful vertebral bone metastases: A prospective study

    Directory of Open Access Journals (Sweden)

    Dipanjan Majumder

    2012-01-01

    Conclusions: Different fractionation of radiation has same response and toxicity in treatment of vertebral bone metastasis. Single fraction RT may be safely used to treat these cases as this is more cost effective and less time consuming. Studies may be conducted to find out particular subgroup of patients to be benefitted more by either fractionation schedule; however, our study cannot comment on that issue.

  10. Severe toxic osteoblastoma of the humerus associated with diffuse periostitis of multiple bones

    Energy Technology Data Exchange (ETDEWEB)

    Dale, S. [Dept. of Radiology, Princess Margaret Hospital for Children, Subiaco, WA (Australia); Breidahl, W.H. [Dept. of Diagnostic Radiology, Royal Perth Hospital, Perth, WA (Australia); Baker, D. [Paediatric Oncology Unit, Princess Margaret Hospital, Subiaco, WA (Australia); Robbins, P.D. [PathCentre, QE 11 Medical Centre, Nedlands, WA (Australia); Sundaram, M. [Department of Radiology, Mayo Clinic, First Street SW 200, 55905 Rochester, MN (United States)

    2001-08-01

    Toxic osteoblastoma is a rare variant of an uncommon primary bone tumour that has been described only once before in the world medical literature. It is characterised by systemic features including fever, weight loss and a striking diffuse periostitis in association with an osteoblastoma, resulting in delayed diagnosis. Early recognition of this condition could prevent inappropriate therapies and reduce morbidity. (orig.)

  11. Multiple flexible intramedullary nailing for the treatment of humeral bone cysts

    Directory of Open Access Journals (Sweden)

    Guity M

    2007-06-01

    Full Text Available Background: Simple bone cyst is a common benign lesion in the proximal humerus, especially in prepubertal children. Up to 75 percent of patients with the bone cyst have a pathologic fracture and the most significant complication is recurrent pathologic fracture. Since the process of spontaneous healing of these fractures is rare, treatment is required. Ideal treatment for simple bone cyst should stabilize pathologic fractures, assist healing and provide a quick return to normal activity with reduced complication and recurrence. Methods: In this descriptive case series study, 24 patients with simple bone cysts of the humerus were selected for retrograde flexible intramedullary nailing from the lateral cortex of the distal humerus, since 2000 to 2005 at Imam Khomeini Hospital, Tehran. The mean age of the patients was 14.4 years, ranging from 6-39 years. Results were evaluated by plain radiography using the classification system of Capanna et al. Results: The mean duration of follow up for 23 of the patients was 31 (9-51 months. One patient with short-term of follow-up was excluded. Of these patients, 91.3% were healed either completely (65.2% or with residual minor defect (26.1%. Only one cyst (4.3% persisted with no response to treatment and one patient (4.3% had a recurrence of the cyst. However, there was no instance of recurrent pathologic fracture among these patients. Conclusion: This study shows that flexible intramedullary nailing is an effective treatment for humeral simple bone cysts that reduces the chance of complication, recurrence of cyst or pathologic fracture. This technique provides sufficient stability for quick return to normal activity.

  12. Vitamin D deficiency and reduced bone mineral density in multiple sclerosis: effect of ambulatory status and functional capacity.

    Science.gov (United States)

    Ozgocmen, Salih; Bulut, Serpil; Ilhan, Nevin; Gulkesen, Arif; Ardicoglu, Ozge; Ozkan, Yusuf

    2005-01-01

    Multiple sclerosis (MS) is a chronic disease and a major cause of disability in young adults. The aims of this study were to assess bone mass in patients with MS in comparison to healthy age- and sex-matched controls, and to evaluate factors influencing bone mineral density (BMD), and the relationship of the pain threshold at peripheral and axial sites with BMD in MS. Thirty-one patients with MS and 30 matched healthy controls participated in the study. The Kurtzke expanded disability status scale (EDSS) and the functional independence measure (FIM) were used to scale disability, mobility, and functional status. Serum 25(OH) vitamin D levels were measured. BMD was measured using dual X-ray absorptiometry (DXA). MS patients had significantly lower BMD at the lumbar spine (L2-L4) and femur trochanter compared to the matched controls. BMD of the lumbar spine was nearly 1 SD lower in MS patients compared with the healthy reference population (Z scores). MS patients had significantly lower vitamin D levels (17.3 ng/ml vs 43.1 ng/ml; P sunlight exposure and to increase their mobility. Specific strengthening exercises for hip and back muscles in MS patients would have a substantial impact on bone density, osteoporosis, fracture risk, and mobility.

  13. Correspondence between flat aberrant crypt foci and mucin-depleted foci in rodent colon carcinogenesis.

    Science.gov (United States)

    Femia, Angelo Pietro; Paulsen, Jan Erik; Dolara, Piero; Alexander, Jan; Caderni, Giovanna

    2008-01-01

    Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) are preneoplastic lesions identified in the colon of carcinogen-treated rodents stained with methylene blue (MB) and high iron diamine-alcian blue (HID-AB), respectively. The correspondence between flat ACF and MDF in the same colon of Min mice treated with azoxymethane (AOM) and of F344 rats treated with 1,2-dimethylhydrazine (DMH) was explored. The position of each flat ACF was recorded on a digitally constructed photographic map of the MB-stained colon. The same colons were then stained with HID-AB and the position of each MDF was compared with that of flat ACF. The fraction of coincident lesions, identified as both flat ACF and MDF with the two staining methods, was 57% and 42%, in the Min mice and F344 rats, respectively. Flat ACF or MDF not coincident with the two staining methods were either undetectable or ACF with one of the two methods. Flat ACF and MDF show considerable, but not total, overlap.

  14. Multiple Eruptive Sebaceous Hyperplasia Secondary to Cyclosporin in a Patient with Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Begonia Cortés

    2016-11-01

    Full Text Available Many cutaneous complications have been described in patients treated with cyclosporin. Alterations of the pilosebaceous unit such as hypertrichosis are particularly frequent. However, the occurrence of sebaceous hyperplasia is exceptional. These lesions seem to be specific to cyclosporin rather than secondary to immunosuppression. Here, we report an exceptional case of eruptive and disseminated sebaceous hyperplasia arising in a bone marrow transplant recipient only a few months after starting immunosuppressive treatment with cyclosporin.

  15. Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients

    DEFF Research Database (Denmark)

    Bieghs, Liesbeth; Brohus, Malene; Kristensen, Ida B

    2016-01-01

    ), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and 125I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5-3.8 fold) and decrease in intact IGFBP-3 (0.6-0.5 fold......) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP...

  16. Case report demonstrating effectiveness of sorafenib in multiple lung and bone metastases of renal cell carcinoma

    OpenAIRE

    HOSHI, MANABU; OEBISU, NAOTO; Takada, Jun; IWAI, TDASHI; Nakamura, Hiroaki

    2015-01-01

    The current study presents the case of a 59-year-old male with advanced-stage renal cell carcinoma and bone metastases in the proximal femur and ilium (cT3aN3M1; stage IV). Resection of the primary renal cell cancer and palliative surgery with a γ-nail for an impending fracture of the right proximal femur were performed, followed by radiotherapy. Sorafenib, a multi-kinase inhibitor that blocks the raf and tyrosine kinases of the vascular endothelial and platelet-derived growth factor receptor...

  17. Stable Isotopic Shifts in Fish Bones from Multiple Archeological Coastal Middens in Penobscot Bay, Maine

    Science.gov (United States)

    Harris, C.; Johnson, B.; Ambrose, W. G.; Bourque, B.; Dostie, P.; Crowley, E.

    2010-12-01

    The carbon and nitrogen stable isotope compositions of collagen extracted from well-preserved archeological fish bones has the potential to provide useful information on fish diets and food web dynamics over time. Previous work on the Turner Farm archaeological site in Penobscot Bay, Gulf of Maine, reveals significant shifts in fish diets have occurred since European colonization (post 1620’s). The objective of the present study was to analyze samples from other archaeological sites within Penobscot Bay to characterize the spatial extent of the isotopic shift measured at Turner Farm. Stratified cod, flounder, and sculpin bones were analyzed from eight coastal middens located approximately 50km apart from one another within Penobscot Bay. The bones were sampled from three time horizons (0kya, 0.5-1kya, and 2.2-2.4kya). All bone samples were demineralized in 0.2M HCl at 4°C for 2 to 7 days and then extracted in 0.25M NaOH at 4°C for 1 to 2 hours. After freeze-drying, the bulk isotopic composition of each sample was analyzed using the EA-IRMS. In all stratigraphic horizons analyzed, cod were more enriched in δ13C and δ15N than sculpin, and flounder were the most depleted in δ13C and δ15N . However, the isotopic offsets between the fish species decreased from 2.4kya to the present. The nitrogen isotope composition was relatively constant over time and space for all species, implying that trophic levels for the fishes analyzed have not changed significantly in Penobscot Bay for the last 2,400 years. The carbon isotope composition also appears to be constant spatially in Penobscot Bay, however, the modern signal was more depleted than the paleo signal in all three species. The difference between the modern and paleo δ13C is ~5‰ for cod and flounder, and ~9‰ for sculpin. These shifts may, in part, be explained by decreases in both primary producer and prey species diversity, as kelp forests replace eelgrass beds in the Gulf of Maine.

  18. Parathyroid and bone imaging in primary hyperparathyroidism

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-Sen; LU Han-Kui; LUO Quan-Yong; CHEN Li-Bo; MA Ji-Xiao

    2004-01-01

    Skeletal derangements occur quite often in patient with primary hyperparathyroidism (PHPT). We investigated parathyroid and bone imagings in 59 cases of pathologically proven PHPT. Forty-nine cases were pathologically proven parathyroid adenomas; 8 presented hyperplasia and the other 2 were adenocarcinomas. Parathyroid imaging (early phase imaging, EPI) was conducted at 30 min after injecting 740~925MBq 99mTc-MIBI and 2~3h later (delayed phase imaging, DPI) separately. The following thyroid imagings were performed at the same posture 10 min after intravenous injection of 74~111MBq 99mTcO4-. The 99mTc- MIBI subtraction imaging data were obtained by subtracting thyroid imaging from that of DPI. Among 49 cases of proven hyperparathyroid adenoma 45 yielded positive imagings. Eight cases with hyperplasia gave negative results. The results were positive in 2 cases of parathyroid adenocarcinoma. Results of 99mTc-MDP/bone imaging: 35 cases of hyperparathyroid adenocarcinoma (disease duration 1-6 months) showed normal bone images, while 14 cases showed superscan images, course being 4-12 months. Bone imaging for 2 cases of adenocarcinoma showed multiple, radioactive aggregated foci (brown tumor imaging); course lasting 10-24 months. The results of bone imaging in 8 cases of hyperplasia/ hyperparathyroidism were normal. It was concluded that diagnostic accuracy for parathyroid was 79.6% and for parathyroid adenoma was 91.8%, and the technique has no diagnostic value for hyperplasia. The 99mTc-MDP / bone imaging results for PHPT can be classified into three categories, i.e. normal, superscan and brown tumor. The imaging results correlated well with the different categories and degrees of bone damage, the duration of clinical course and the pathological types. Therefore, it's important to use bone imaging data in association with therapy to reflect the stage and progress of PHPT.

  19. A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

    Institute of Scientific and Technical Information of China (English)

    Hong Wei; Xinchun Ding; Jiangong Ren; Ka Liu; Pingping Tan; Daquan Li; Runlin Z.Ma

    2008-01-01

    Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im-munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura (ITP) has not been fullyunderstood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or plateletdestruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into theBalb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini-mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h (6 days). Final homeostasis reached atapproximately 408 h (17 days), following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed andcompared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration ofmRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be-tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when plateletnumber reached the maximum (144 h). In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleentissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Ourresults provided the supportive evidence that expression of the above seven genes are more related to negative regulation of plateletnumber in spleen tissue, at least in the model animals.

  20. Multiple Myeloma Symptoms

    Science.gov (United States)

    ... Treatment Center Finder Home » About Multiple Myeloma » Symptoms Multiple Myeloma Symptoms Multiple myeloma symptoms may vary by patient, ... to be managed or prevented. The most common multiple myeloma symptoms may include: Bone pain or bone fractures ...

  1. The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells.

    Science.gov (United States)

    Wang, Jinheng; De Veirman, Kim; De Beule, Nathan; Maes, Ken; De Bruyne, Elke; Van Valckenborgh, Els; Vanderkerken, Karin; Menu, Eline

    2015-12-22

    Exosomes, extracellular nanovesicles secreted by various cell types, modulate the bone marrow (BM) microenvironment by regulating angiogenesis, cytokine release, immune response, inflammation, and metastasis. Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells play crucial roles in MM development. We previously reported that BMSC-derived exosomes directly promote MM cell growth, whereas the other possible mechanisms for supporting MM progression by these exosomes are still not clear. Here, we investigated the effect of BMSC-derived exosomes on the MM BM cells with specific emphasis on myeloid-derived suppressor cells (MDSCs). BMSC-derived exosomes were able to be taken up by MM MDSCs and induced their expansion in vitro. Moreover, these exosomes directly induced the survival of MDSCs through activating STAT3 and STAT1 pathways and increasing the anti-apoptotic proteins Bcl-xL and Mcl-1. Inhibition of these pathways blocked the enhancement of MDSC survival. Furthermore, these exosomes increased the nitric oxide release from MM MDSCs and enhanced their suppressive activity on T cells. Taken together, our results demonstrate that BMSC-derived exosomes activate MDSCs in the BM through STAT3 and STAT1 pathways, leading to increased immunosuppression which favors MM progression.

  2. Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Maximilian; Hillengass, Jens [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Moehler, Thomas M.; Ritsch, Judith; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Baeuerle, Tobias [University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Zechmann, Christian M. [Rinecker Proton Therapy, Muenchen (Germany); Wagner, Barbara; Hose, Dirk [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Jauch, Anna [University of Heidelberg, Institute of Human Genetics, Heidelberg (Germany); Kunz, Christina; Hielscher, Thomas [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Laue, Hendrik [Fraunhofer MEVIS, Bremen (Germany); Goldschmidt, Hartmut [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); National Center for Tumor Diseases, Heidelberg (Germany)

    2016-05-15

    Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant k{sub ep}. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and k{sub ep}. Additionally, A was negatively correlated with haemoglobin levels and k{sub ep} was positively correlated with LDH levels. Higher baseline k{sub ep} values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. (orig.)

  3. Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice.

    Science.gov (United States)

    Wang, D; Fløisand, Y; Myklebust, C V; Bürgler, S; Parente-Ribes, A; Hofgaard, P O; Bogen, B; Tasken, K; Tjønnfjord, G E; Schjesvold, F; Dalgaard, J; Tveita, A; Munthe, L A

    2017-02-24

    Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner in vitro. MM cells had retained the ability to activate Th cells that reciprocated and stimulated MM cell proliferation. Autologous BM Th cells supported MM cell growth in xenografted mice and were found in close contact with MM cells. MM cells secreted chemokines that attracted Th cells, secretion was augmented by CD40-stimulation. Within 14 days of culture of whole bone marrow aspirates in autologous serum, MM cells and Th cells mutually stimulated each other, and MM cells required Th cells for further expansion in vitro and in mice. The results suggest that Th cells may support the expansion of MM cells in patients.Leukemia accepted article preview online, 24 February 2017. doi:10.1038/leu.2017.69.

  4. In anemia of multiple myeloma hepcidin is induced by increased bone-morphogenetic protein-2

    Science.gov (United States)

    Hepcidin is the principal iron-regulatory hormone and pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. We showed that MM patients had increased serum hepcidin, which inversely correlated with hemoglobin, suggesting that hepcidin contrib...

  5. Understanding the persistence of plague foci in Madagascar.

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    2013-11-01

    Full Text Available Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  6. Understanding the persistence of plague foci in Madagascar.

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-11-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  7. Understanding the Persistence of Plague Foci in Madagascar

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar. PMID:24244760

  8. Capturing domain knowledge from multiple sources: the rare bone disorders use case

    OpenAIRE

    Groza, Tudor; Tudorache, Tania; Peter N Robinson; Zankl, Andreas

    2015-01-01

    Background Lately, ontologies have become a fundamental building block in the process of formalising and storing complex biomedical information. The community-driven ontology curation process, however, ignores the possibility of multiple communities building, in parallel, conceptualisations of the same domain, and thus providing slightly different perspectives on the same knowledge. The individual nature of this effort leads to the need of a mechanism to enable us to create an overarching and...

  9. Cell multiplication, apoptosis and p-Akt protein expression of bone mesenchymal stem cells of rat under hypoxia environment

    Institute of Scientific and Technical Information of China (English)

    Hongliang Kong; Ningning Liu; Xin Huo; Bo Wang; Haipeng Zhang; Mingyu Gao; Guoxian Qi

    2007-01-01

    Objective :To elucidate whether cell multiplication, apoptosis, glucose intake and p-Akt protein expression of bone Mesenchymal Stem Cells(MSCs) of rats is influenced by a hypoxic environment ex vivo. Methods:Passage 3 of bone marrow MSCs taken from Wistar rats, were cultured in a culturing chamber with 94%N2,1%O2, 5%CO2 at 37℃. At different hypoxia time points, 0,0.5,1,4 and 8 h, glucose uptake was assayed by using radiation isotope 3H-G, Apoptotic Rate(AR) and dead rate(DR) were analyzed by flow cytometry(FCM) after Annexin V/PI staining, cell multiplication(by MTT methods) and p-Akt protein by immunocytochemistry and western blot. Results:Assay for CD29+,CD44+,CD71+,CD34-, Tn T+(after 5-azacytidine agent inducing) and ALP+(after bone differentiation agent inducing) suggested these bone-derived cells were MSCs. The 3H-G intaking ratio (CPM/flask value:157 ± 11,110 ± 11,107 ± 13,103 ± 10,100 ± 9 and 98 ± 10) of MSCs at different hypoxia time points, significantly decreased compared to that of normoxia(P < 0.01) and tended to descend slowly with hypoxia time duration, for which there was no statistical significance(P > 0.05). The AR(0.09 ± 2.03%,12.9 ± 1.72%,13.7 ± 2.26%,13.8 ± 3.01% ,14.1 ± 2.78% and 14.7 ±4.01% at 0,0.5,1,4 and 8 h,respectively,P < 0.01) and DR (0.04 ± 1.79% ,0.93 ± 1.85% ,3.11 ± 2.14%,4.09 ± 2.36% ,4.72 ±2.05% and 4.91 ± 3.72% at 0,0.5,1,4 and 8 h, respectively, P < 0.05) at different hypoxia time points significantly increased compared to those time in normoxia; The AR further went up with time (P < 0.05), however there was no statistical significance(P > 0.05) for the DR. Optical absorption value of MTT methods at different hypoxia time points significantly decreased compared to those with a corresponding normoxia time (P < 0.01 ) and degraded with time (in an hypoxic environment -P < 0.01 ).IOD of p-Akt protein of MSCs at different hypoxia time points significantly increased (0.367 ± 0.031,0.556 ± 0

  10. Multiple Tumor Types May Originate from Bone Marrow-Derived Cells

    Directory of Open Access Journals (Sweden)

    Chunfang Liu

    2006-09-01

    Full Text Available It was believed that tumors originated from the transformation of their tissue-specific stem cells. However, bone marrow-derived cells (BMDCs, which possess an unexpected degree of plasticity and often reside in other tissues, might also represent a potential source of malignancy. To study whether BMDCs play a role in the source of other tumors, BMDCs from mice were treated with 3-methycholanthrene until malignant transformation was achieved. Here we show that transformed BMDCs could form many tumor types, including epithelial tumors, neural tumors, muscular tumors, tumors of fibroblasts, blood vessel endothelial tumors, and tumors of poor differentiation in vivo. Moreover, a single transformed BMDC has the ability to self-renew, differentiate spontaneously into various types of tumor cells in vitro, express markers associated with multipotency, and form teratoma in vivo. These data suggest that multipotent cancer stem cells seemed to originate from transformed BMDCs. Conclusively, these findings reveal that BMDCs might be a source of many tumor types, even teratoma. In addition, multipotent cancer stem cells might originate from malignant transformed BMDCs.

  11. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Hou, Zong-liu; Liu, Ying; Mao, Xi-Hong; Wei, Chuan-yu; Meng, Ming-yao; Liu, Yun-hong; Zhuyun Yang, Zara; Zhu, Hongmei; Short, Martin; Bernard, Claude; Xiao, Zhi-cheng

    2013-01-01

    There is currently great interest in the use of mesenchymal stem cells as a therapy for multiple sclerosis with potential to both ameliorate inflammatory processes as well as improve regeneration and repair. Although most clinical studies have used autologous bone marrow-derived mesenchymal stem cells, other sources such as allogeneic umbilical cord-derived cells may provide a more accessible and practical supply of cells for transplantation. In this case report we present the treatment of aggressive multiple sclerosis with multiple allogenic human umbilical cord-derived mesenchymal stem cell and autologous bone marrow-derived mesenchymal stem cells over a 4 y period. The treatments were tolerated well with no significant adverse events. Clinical and radiological disease appeared to be suppressed following the treatments and support the expansion of mesenchymal stem cell transplantation into clinical trials as a potential novel therapy for patients with aggressive multiple sclerosis.

  12. Three-dimensional array foci of generalized Fibonacci photon sieves

    CERN Document Server

    Zhang, Junyong; Zhu, Jianqiang; Lin, Zunqi

    2015-01-01

    We present a new kind of photon sieves on the basis of the generalized Fibonacci sequences. The required numbers and locations of axial foci can be designed by generalized Fibonacci photon sieves (GFiPS). Furthermore, the three-dimensional array foci can be controllable and adjustable by the optical path difference scaling factor (OPDSF) when the amplitude modulation is replaced with the phase modulation. Multi-focal technologies can be applied to nano-imaging, THZ, laser communications, direct laser writing, optical tweezers or atom trapping, etc.

  13. Remitting–relapsing multiple sclerosis patient refractory to conventional treatments and bone marrow transplantation who responded to natalizumab

    Directory of Open Access Journals (Sweden)

    Athanasia Mouzaki

    2010-09-01

    Full Text Available Athanasia Mouzaki1, Maria Koutsokera2, Zoe Dervilli1, Maria Rodi1, Dimitra Kalavrizioti1,3, Nikolaos Dimisianos2, Ioannis Matsoukas3, Panagiotis Papathanasopoulos21Division of Hematology, Department of Internal Medicine, 2Neurology Clinic, Medical School and University Hospital, 3Department of Chemistry, University of Patras, Patras, GreeceAbstract: Bone marrow transplantation (BMT was introduced as a treatment option 15 years ago for severe, drug-resistant multiple sclerosis (MS. Up until now, BMT has been undertaken in relatively few patients worldwide, with moderate success, and recent studies suggest that patients with early, highly aggressive MS benefit most from this treatment. In this work, we determined peripheral blood lymphocyte populations in a patient (patient A with remitting–relapsing multiple sclerosis (RR-MS, refractory to conventional treatments, and who underwent BMT, relapsed, and has been treated with natalizumab for the last 22 months. Eleven other RR-MS patients in the acute phase of the disease, untreated or treated with interferon-beta, and 20 healthy subjects served as controls. Natalizumab treatment in patient A resulted in lymphocytosis and increased levels of CD20+/CD20+CD5+ B cells and T regulatory cells (Tregs. The patient maintained relatively low levels of T cells, T helper cells, memory T helper cells, and naive cytotoxic T cells, and very low levels of naive T helper cells and natural killer cells throughout. The Tregs of patient A post-treatment with natalizumab responded well in culture to a peptide mapping to a myelin basic protein antigenic epitope (mean 42% increase compared with Tregs of healthy controls (mean 15% increase whereas Tregs of the RR-MS controls or patient A prenatalizumab treatment either did not respond or responded adversely to the peptide (mean 3% and 21% decreases, respectively. Since the beginning of natalizumab treatment, patient A has had no relapses, and his Expanded Disability

  14. Single- versus multiple-fraction radiotherapy in patients with painful bone metastases: cost-utility analysis based on a randomized trial.

    NARCIS (Netherlands)

    Hout, W.B. van den; Linden, Y.J.M. van der; Steenland, E.; Wiggenraad, R.G.; Kievit, J.; Haes, J.C.J.M. de; Leer, J.W.H.

    2003-01-01

    BACKGROUND: Radiotherapy is an effective palliative treatment for cancer patients with painful bone metastases. Although single- and multiple-fraction radiotherapy are thought to provide equal palliation, which treatment schedule provides better value for the money is unknown. We compared quality-ad

  15. Fractionated half body irradiation for palliation of multiple symptomatic bone metastases from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sekiguchi, Kenji; Hayashi, Shinya; Sunagawa, Yoshimitsu; Sougawa, Mitsuharu; Nakazawa, Masanori; Yamashita, Takashi (Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital)

    1992-06-01

    This was a phase I-II nonrandomized study that explored the toxicity and response of fractionated half-body irradiation (F-HBI) in patients with multiple symptomatic osseous metastases. The patients had no premedication and received 10 Gy in 5 fractions with a dose rate of 15 cGy/min. At the Cancer Institute Hospital, 9 patients were treated by this technique (1 upper and lower F-HBI, 6 upper F-HBI, 2 lower F-HBI). All patients were female and had adenocarcinomas (8 breast and 1 lung). Adverse effects were myelosuppression, vomiting and partial alopecia. But hematologic toxicity was treated with blood transfusion or G-CSF. All toxicity was transient, and no pneumonitis nor radiation-related deaths occurred. When given as palliation, F-HBI was found to relieve pain in 80% of the patients. In 10% of the patients the pain relief was complete. The mean time to achieve pain relief in responders after F-HBI was 9 days. The pain relief was long-lasting and continued without need of reirradiation for 40% of the remaining patient's life. This treatment modality appears to be well tolerated and effective in patients with multiple symptomatic osseous metastases. The optimal indications, dose and fractionation for F-HBI should be further explored in randomized trials. (author).

  16. Comparison of single versus multiple fractions for palliative treatment of painful bone metastasis: First study from north west India

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2015-01-01

    Full Text Available Background: Bone metastasis is a usual cause of pain in advanced cancer. Conventional radiation schedules require larger hospital stay and thus are not suitable for patients with poor general condition. This prospective observational study aims to compare the pain-relieving efficacy of different radiation fractionation schedules, i.e., 8 Gy administered in a single fraction versus 30 Gy administered in 10 fractions. Materials and Methods: Two hundred and fifty consecutive patients of bone metastasis were evaluated for the study, with 63 patients being excluded due to non-fulfillment of the inclusion criteria. The response to radiotherapy leading to pain relief as per the Visual Analog Scale was recorded at the end of treatment, 8 days, 15 days and 1 month during the follow-up visits. Results: Sixty-two percent of the patients received a single fraction while the remaining received 10 fractions. In the 10-fraction group, overall response was present in 60% of the patients. Stable pain was present in 23% of the patients while 9% patients had progressive pain. At 1 month of completion of treatment, 9% patients were lost to follow-up. In the single-fraction arm, overall response was seen in 58%, stable pain in 27% and progressive pain in 7% of the patients. Six percent of the patients were lost to follow-up. Conclusions: Single-fraction treatment for bony metastasis is as effective as multiple fractions to relieve bony pain and provides treatment convenience to both the patient and the caregiver.

  17. Dosimetry and toxicity of Quadramet for bone marrow ablation in multiple myeloma and other haematological malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, Marissa L.; Webb, Myles; Macfarlane, David J. [Department of Nuclear Medicine, Royal Brisbane Hospital, Herston, Queensland, Q4209 (Australia); Durrant, Simon; Morton, James A.; Allison, Roger [Division of Oncology, Royal Brisbane Hospital, Herston, Queensland (Australia)

    2002-11-01

    Standard treatment regimens for haematological malignancies include myeloablative chemoradiotherapy and subsequent rescue by stem cell transplantation. However, these treatment regimens have significant associated mortality and morbidity, and disease recurrence remains a problem. One alternative approach is the targeted delivery of radiotherapy to the marrow using a bone-seeking agent labelled with an appropriate radioisotope, with the aim of delivering a potentially ablative radiation dose to marrow while minimising non-haematological toxicity. Pharmacokinetics and radiation dosimetry for a commercial preparation of samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP; Quadramet) were evaluated in 43 tracer (average dose 740 MBq) studies of 42 patients with haematological malignancies. Measurements of 24-h retention were also available following infusion of 18-48 GBq in 15 patients. Quadramet cleared rapidly from the tissue, with a median biological half-life of 1.4 h. Activity taken up by the skeleton was firmly bound, with activity decreasing according to physical half-life at 24 h in 29 of the 43 cases. The percentage activity retained in the skeleton at 24 h with tracer doses was high (62%{+-}13%), although this decreased to approximately 30% with therapy infusions. Because of this decrease in retention, the maximum feasible therapy activity for this formulation of Quadramet is 35 GBq. Median absorbed marrow radiation dose was 0.78 Gy/GBq in tracer studies: the decreased retention at high activities means that this corresponds to a median dose of 12 Gy for 35 GBq administered activity. It is possible to use 24-h retention as a rough guide to marrow dose in individual patients. In tracer studies, median bladder radiation dose was 0.22 Gy/GBq and radiation dose to the liver was very conservatively estimated at 0.2 Gy/GBq. After therapy infusions of up to 50 GBq in 37 patients, non-haematopoietic toxicity was not seen in any patient. In addition

  18. Dosimetry and toxicity of Quadramet for bone marrow ablation in multiple myeloma and other haematological malignancies.

    Science.gov (United States)

    Bartlett, Marissa L; Webb, Myles; Durrant, Simon; Morton, A James; Allison, Roger; Macfarlane, David J

    2002-11-01

    Standard treatment regimens for haematological malignancies include myeloablative chemoradiotherapy and subsequent rescue by stem cell transplantation. However, these treatment regimens have significant associated mortality and morbidity, and disease recurrence remains a problem. One alternative approach is the targeted delivery of radiotherapy to the marrow using a bone-seeking agent labelled with an appropriate radioisotope, with the aim of delivering a potentially ablative radiation dose to marrow while minimising non-haematological toxicity. Pharmacokinetics and radiation dosimetry for a commercial preparation of samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP; Quadramet) were evaluated in 43 tracer (average dose 740 MBq) studies of 42 patients with haematological malignancies. Measurements of 24-h retention were also available following infusion of 18-48 GBq in 15 patients. Quadramet cleared rapidly from the tissue, with a median biological half-life of 1.4 h. Activity taken up by the skeleton was firmly bound, with activity decreasing according to physical half-life at 24 h in 29 of the 43 cases. The percentage activity retained in the skeleton at 24 h with tracer doses was high (62%+/-13%), although this decreased to approximately 30% with therapy infusions. Because of this decrease in retention, the maximum feasible therapy activity for this formulation of Quadramet is 35 GBq. Median absorbed marrow radiation dose was 0.78 Gy/GBq in tracer studies: the decreased retention at high activities means that this corresponds to a median dose of 12 Gy for 35 GBq administered activity. It is possible to use 24-h retention as a rough guide to marrow dose in individual patients. In tracer studies, median bladder radiation dose was 0.22 Gy/GBq and radiation dose to the liver was very conservatively estimated at 0.2 Gy/GBq. After therapy infusions of up to 50 GBq in 37 patients, non-haematopoietic toxicity was not seen in any patient. In addition

  19. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease

    Directory of Open Access Journals (Sweden)

    Coluzzi F

    2015-05-01

    Full Text Available Flaminia Coluzzi,1,2 Robert B Raffa,3 Joseph Pergolizzi,4 Alessandra Rocco,1 Pamela Locarini,1 Natalia Cenfra,5 Giuseppe Cimino,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Unit of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA; 4Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy Context: Myeloma bone disease (MBD is a devastating complication of multiple myeloma that leads to severe pain. Objectives: The aim of this study was to evaluate the efficacy and tolerability of tapentadol prolonged release (PR in the management of patients with MBD suffering from moderate-to-severe cancer pain. Methods: A 12-week prospective study was carried out in 25 opioid-naïve MBD patients. Patients initially received twice-daily doses of tapentadol PR 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity. The following parameters were recorded at weekly intervals for 4 weeks, and then at weeks 8 and 12: pain, opioid-related adverse effects, use of other analgesics, DN4 (Douleur Neuropathique 4 score. Quality of life (SF-36 [36-item short-form health survey] was measured at baseline and at final evaluation. Results: Of 25 patients, 22 completed the study. Pain intensity significantly decreased from baseline to all the week intervals (P<0.01. Quality of life significantly improved with respect to all SF-36 subscale parameters (P<0.01, and so did both the physical and mental status (P<0.01. Tapentadol PR significantly reduced DN4 mean value (P<0.01 and the number of patients with neuropathic component

  20. Pregnant ewes exposed to multiple endocrine disrupting pollutants through sewage sludge-fertilized pasture show an anti-estrogenic effect in their trabecular bone

    Energy Technology Data Exchange (ETDEWEB)

    Lind, P. Monica, E-mail: Monica.Lind@medsci.uu.se [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Ullerakersvaegen 40, 751 85 Uppsala (Sweden); Oberg, Denise [Department of Environmental Toxicology, Uppsala University, Uppsala (Sweden); Larsson, Sune [Department of Orthopaedics, Uppsala University, Uppsala (Sweden); Kyle, Carol E. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Orberg, Jan [Department of Environmental Toxicology, Uppsala University, Uppsala (Sweden); Rhind, Stewart M. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom)

    2010-05-01

    Pregnant ewes were maintained on pastures fertilized, twice yearly, with either sewage sludge (2.25 tonnes dry matter/ha; Treated; T) or inorganic fertilizer containing equivalent amounts of nitrogen (Control; C), to determine effects on maternal and fetal bone structures, density and mechanical properties of exposure to environmental concentrations of multiple endocrine disrupting compounds (EDCs) and heavy metal pollutants. The ewes were maintained on the respective pastures from the age of about 8 months until they were 4-6 years of age and they were slaughtered at 110 d gestation. Metaphyseal parts of adult ewe femurs exhibited a significantly reduced mean, total cross sectional area (CSA, - 4%; p < 0.05), lower trabecular bone mineral content (BMC, mg/mm; - 18%; p < 0.05), trabecular bone mineral density (BMD, mg/cm{sup 3}, - 8.0%; p < 0.05) and trabecular CSA, mm{sup 2}, - 11.1%; p < 0.05) in T compared with C animals. Femurs of T ewes were stronger than those of C ewes but this may reflect greater body weights. At the mid-diaphyseal part of the fetal bones, there was a reduction in endosteal circumference (- 6.7%, p < 0.05) and marrow cavity area (- 13.8%, p < 0.05) in the female T fetuses compared with female C fetuses. In the male fetuses the mid-diaphyseal part total bone mineral content was higher (+ 3.0%, p < 0.05) in T than in C animals. No treatment difference in biomechanical bending was detected in the fetuses. It is concluded that ewes grazing pasture fertilized with sewage sludge exhibited an anti-estrogenic effect on their trabecular bone in the form of reduced mineral content and density, despite increased body weight. It is suggested that human exposure to low levels of multiple EDCs may have implications for bone structure and human health.

  1. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A; Oturai, Ditte Bang; Sørensen, P S;

    2015-01-01

    BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate the importa......BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate...... the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. METHODS: A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference...... population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. RESULTS: Osteopenia was present in 38...

  2. Molecular cytogenetic aberrations in Tunisian patients with multiple myeloma identified by cIg-FISH in fixed bone marrow cells.

    Science.gov (United States)

    Gmidène, A; Avet-Loiseau, H; Sennana, H; Ben Abdallah, I; Khlif, A; Meddeb, B; Elloumi, M; Saad, A

    2012-01-01

    Cytogenetic studies in multiple myeloma (MM) are hampered by the hypo-proliferative nature of plasma cells. In order to circumvent this problem, we have used a combination of immunolabeling of cytoplasmic Ig light chains (λ or κ) and FISH (cIg-FISH), which allowed a comprehensive detection of the most common and/or recurrent molecular cytogenetic aberrations on fixed bone marrow cells of 70 Tunisian patients. Translocations involving the chromosome 14q32 region were observed in 32 cases (45.7%), including 18 cases with a t(11;14), 8 cases with a t(4;14), and 2 cases with a t(14;16). Deletions of the 13q14 region (D13S319/RB1) were detected in 18.6%, and deletions of the 17p13 region (TP53) in 5.7% of the cases, respectively. Of all patients with a D13S319/RB1 deletion, 61.5% also carried a 14q32 translocation, whereas TP53 deletions were associated with a t(11;14) in 2 cases (50%) and a D13S319 deletion in 1 case (25%). Our results suggest that there is a correlation between the presence of 14q32 translocations and chromosome 13q14 deletions in MM patients and that cIg-FISH is more sensitive as compared to conventional karyotyping in detecting molecular cytogenetic abnormalities in this disease. Copyright © 2011 S. Karger AG, Basel.

  3. The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications.

    Science.gov (United States)

    Podar, Klaus; Zimmerhackl, Alexander; Fulciniti, Mariateresa; Tonon, Giovanni; Hainz, Ursula; Tai, Yu-Tzu; Vallet, Sonia; Halama, Niels; Jäger, Dirk; Olson, Dian L; Sattler, Martin; Chauhan, Dharminder; Anderson, Kenneth C

    2011-11-01

    Recent advances regarding the introduction of anti-adhesion strategies as a novel therapeutic concept in oncology hold great promise. Here we evaluated the therapeutic potential of the new-in-class-molecule selective-adhesion-molecule (SAM) inhibitor Natalizumab, a recombinant humanized IgG4 monoclonal antibody, which binds integrin-α4, in multiple myeloma (MM). Natalizumab, but not a control antibody, inhibited adhesion of MM cells to non-cellular and cellular components of the microenvironment as well as disrupted the binding of already adherent MM cells. Consequently, Natalizumab blocked both the proliferative effect of MM-bone marrow (BM) stromal cell interaction on tumour cells, and vascular endothelial growth factor (VEGF)-induced angiogenesis in the BM milieu. Moreover, Natalizumab also blocked VEGF- and insulin-like growth factor 1 (IGF-1)-induced signalling sequelae triggering MM cell migration. In agreement with our in vitro results, Natalizumab inhibited tumour growth, VEGF secretion, and angiogenesis in a human severe combined immunodeficiency murine model of human MM in the human BM microenvironment. Importantly, Natalizumab not only blocked tumour cell adhesion, but also chemosensitized MM cells to bortezomib, in an in vitro therapeutically representative human MM-stroma cell co-culture system model. Our data therefore provide the rationale for the clinical evaluation of Natalizumab, preferably in combination with novel agents (e.g. bortezomib) to enhance MM cytotoxicity and improve patient outcome.

  4. Human ESC-Derived MSCs Outperform Bone Marrow MSCs in the Treatment of an EAE Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Xiaofang Wang

    2014-07-01

    Full Text Available Current therapies for multiple sclerosis (MS are largely palliative, not curative. Mesenchymal stem cells (MSCs harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs. Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE.

  5. Radius bone strength in bending, compression, and falling and its correlation with clinical densitometry at multiple sites.

    Science.gov (United States)

    Lochmüller, Eva-Maria; Lill, Christoph A; Kuhn, Volker; Schneider, Erich; Eckstein, Felix

    2002-09-01

    This study comprehensively analyzes the ability of site-specific and nonsite-specific clinical densitometric techniques for predicting mechanical strength of the distal radius in different loading configurations. DXA of the distal forearm, spine, femur, and total body and peripheral quantitative computed tomography (pQCT) measurements of the distal radius (4, 20, and 33%) were obtained in situ (with soft tissues) in 129 cadavers, aged 80.16 +/- 9.8 years. Spinal QCT and calcaneal quantitative ultrasound (QUS) were performed ex situ in degassed specimens. The left radius was tested in three-point bending and axial compression, and the right forearm was tested in a fall configuration, respectively. Correlation coefficients with radius DXA were r = 0.89, 0.84, and 0.70 for failure in three-point bending, axial compression, and the fall simulation, respectively. The correlation with pQCT (r = 0.75 for multiple regression models with the fall) was not significantly higher than for DXA. Nonsite-specific measurements and calcaneal QUS displayed significantly (p radius, nonsite-specific measurements are less accurate for this purpose, and QUS adds only little independent information to site-specific bone mass. Therefore, the noninvasive diagnosis of loss of strength at the distal radius should rely on site-specific measurements with DXA or pQCT and may be the earliest chance to detect individuals at risk of osteoporotic fracture.

  6. PMEL EcoFOCI Chukchi Sea profile data, 2010-2012

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Pacific Marine Environmental Laboratory (PMEL) Fisheries-Oceanography Cooperative Investigations (FOCI) Chukchi Sea. PMEL EcoFOCI data from a local source.

  7. Multiple bony lesions other than femoral heads on {sup 99m}Tc-MDP bone scan in patients with avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Young; Yang, Seoung Oh; Moon, Dae Hyuk; Ryu, Jin Sook; Weon, Young Cheol; Shin, Myung Jin; Lee, Soo Ho; Lee, Hee Kyung [Asan Medical Center, Ulsan Univ. College of Medicine, Ulsan (Korea, Republic of); Chun, Hae Kyung [St. Francisco Hospital, Seoul (Korea, Republic of)

    1997-03-01

    To evaluate the clinical significance of the multiple increased uptake lesions other than in femoral heads as seen on whole body bone scan in patients with avascular necrosis of femoral heads. One hundred and seventy three patients with clinical diagnosis of avascular necrosis of the emoral head underwent a bone scan using Tc-99m MDP. Increased uptake lesions other than in femoral heads were evaluated, including frequency and common sites of in volvement, and correlated with clinical information and plain radiographic findings. Two hundred patients without AVN, who had undergone a bone scan, were included as a control group. Increased uptake lesions in extrafemoral head locations were found in 36 of 173 patients(20.8%); the location of 79 lesions was other than the femoral head. This result is statistically different from patients without avascular necrosis of femoral head(p<0.0001). The most common site of involvement was the knee joint area(62.5%). Other lesions were located in the mid-shafts of the long bones of the lower extremities, calcaneus, proximal humerus, etc., in order of decreasing frequency. Plain radiographs of 17 lesions were nonspecific, except for three lesions showing definite changes associated with avascular necrosis. The risk factors included alcoholism, the prolonged use of steroids, renal transplantation, herbal medication and working as a working as deep-sea diver. Most patients did not complain of pain, except for two with irreversible osteonecrotic changes as seen on plain radiograph. in patients with avascular necrosis of the femur, increased uptake lesions other than in the femoral head as seen on bone scan, may represent the early stage of osteonecrosis, which shows a characteristic appearance on bone scan. In order to aveid possible misdiagnoses of multiple extrafemoral lesions as bony metastasis or traumatic lesions, in patients with avascular necrosis of the femur these should be carefully evaluated.

  8. Features of direct implantation in chronic foci of odontogenic infection

    Directory of Open Access Journals (Sweden)

    Gudaryan А.А.

    2016-12-01

    Full Text Available The article presents the results of the developed therapeutic and prophylactic complex and efficacy of immediate implantation in 66 patients with chronic foci of odontogenic infection in the periapical region. Objective: to increase preventive measures of inflammatory and infectious complications and optimization of osteo-integrative processes in immediate implantation after tooth extraction, with periapical foci of chronic infection. It was found that the use of the developed medical complex of following up direct implantation includes the use of local photodynamic therapy, platelet, rich in fibrin as a injection and membranes; this allowed to create a favorable background for the prevention of inflammatory and infectious complications in the peri-implant area and created a favorable background for the osseo-integration of implants in 97.1% of the investigated.

  9. [The implantation of bipolar coagulation to remove endometriosis foci].

    Science.gov (United States)

    Sobkiewicz, S; Palatyński, A; Salata, I

    2001-05-01

    The paper compares the results of bipolar coagulation bey means of ERBE ICC 300 diatermy coagulator and WISAP endocoagulator. The results of both types of coagulation were assessed with reference to the changes occurring on peritoneum ligamenti sacro-uterini, Douglas pouch and ovary. The best results of endometriosis foci coagulation were obtained with bipolar ball at 20-30 W; no side effects or feelings of malaise were observed in patients just after the operation or over a longer period of convalescence.

  10. Multistability in Chua's circuit with two stable node-foci

    Energy Technology Data Exchange (ETDEWEB)

    Bao, B. C.; Wang, N.; Xu, Q. [School of Information Science and Engineering, Changzhou University, Changzhou 213164 (China); Li, Q. D. [Research Center of Analysis and Control for Complex Systems, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China)

    2016-04-15

    Only using one-stage op-amp based negative impedance converter realization, a simplified Chua's diode with positive outer segment slope is introduced, based on which an improved Chua's circuit realization with more simpler circuit structure is designed. The improved Chua's circuit has identical mathematical model but completely different nonlinearity to the classical Chua's circuit, from which multiple attractors including coexisting point attractors, limit cycle, double-scroll chaotic attractor, or coexisting chaotic spiral attractors are numerically simulated and experimentally captured. Furthermore, with dimensionless Chua's equations, the dynamical properties of the Chua's system are studied including equilibrium and stability, phase portrait, bifurcation diagram, Lyapunov exponent spectrum, and attraction basin. The results indicate that the system has two symmetric stable nonzero node-foci in global adjusting parameter regions and exhibits the unusual and striking dynamical behavior of multiple attractors with multistability.

  11. Inter-observer agreement for the evaluation of bone involvement on Whole Body Low Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Zacchino, M.; Minetti, V.; Dore, R.; Calliada, F. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Institute of Radiology, Pavia (Italy); Bonaffini, P.A.; Nasatti, A.; Sironi, S. [University of Milano Bicocca, San Gerardo Hospital, Department of Diagnostic Radiology, Monza (Italy); Corso, A. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Division of Hematology, Pavia (Italy); Tinelli, C. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Service of Biometry and Statistics, Pavia (Italy)

    2015-11-15

    We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. According to Cohen's criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers' experience. (orig.)

  12. Acanthomatous ameloblastoma with atypical foci in five dogs.

    Science.gov (United States)

    Malmberg, Jennifer L; Howerth, Elizabeth W; Powers, Barb E; Schaffer, Paula A

    2017-03-01

    Acanthomatous ameloblastoma is a common, locally invasive, nonmetastasizing tumor of the canine oral cavity. The long-term prognosis for canine acanthomatous ameloblastoma is good if complete excision can be achieved, usually by maxillectomy or mandibulectomy. A variant of acanthomatous ameloblastoma with atypical foci was noted in 5 dogs. There was no age, breed, or sex predisposition. Atypical cells were pleomorphic with a high mitotic rate. They were immunohistochemically negative for cytokeratin, vimentin, melan A, PNL2, CD3, Pax5, CD18, chromogranin A, and synaptophysin. Ultrastructurally, the atypical cells had modest amounts of electron-lucent cytoplasm, abundant rough endoplasmic reticulum, zonula adherens junctions, cleaved or irregular nuclei, and occasional cytoplasmic structures consistent with secretory granules or lysosomes. Complete excision was achieved by maxillectomy or mandibulectomy in 3 dogs; the lesion was incompletely excised in 2 dogs. No ancillary therapy was elected in any patient. No local recurrence or distant metastasis was reported in any case. One patient died of heart failure 20 mo following complete excision; all other patients were alive at last follow-up (average follow-up: 18.8 mo, range: 6-30 mo). The histogenesis of the atypical foci is unclear, but atypical foci within acanthomatous ameloblastoma do not appear to be associated with metastasis or with a poor prognosis relative to acanthomatous ameloblastoma with typical histologic morphology.

  13. Reliability of seizure semiology in patients with 2 seizure foci.

    Science.gov (United States)

    Rathke, Kevin M; Schäuble, Barbara; Fessler, A James; So, Elson L

    2011-06-01

    To determine whether seizure semiology is reliable in localizing and distinguishing seizures at 2 independent brain foci in the same patient. Two masked reviewers localized seizures from 2 foci by their clinical semiology and intracranial electroencephalograms (EEGs). Epilepsy monitoring unit of referral comprehensive epilepsy program. Seventeen consecutive patients (51 seizures) with sufficient video and intracranial EEG data were identified by reviewing medical records of 366 patients older than 10 years. The primary outcome measures were interobserver agreement between the 2 masked reviewers; the proportion of seizures localized by semiology; the proportion of localized seizures concordant with intracranial EEG localization; and comparison between concordant and nonconcordant seizures in latency of intracranial EEG seizure spread. Interobserver agreement was 41% (κ score, 0.16). Only 30 of 51 seizures (59%) were localized by seizure semiology. The focus localized by semiology was concordant with the location of intracranial EEG seizure onset in 16 of 30 seizures (53%). No significant difference was observed between concordant and nonconcordant seizures in relation to the speed with which the EEG discharge spread from the location of seizure onset to another lobar region (P = .09, Wilcoxon rank sum test). Clinical seizure semiology is not as useful as intracranial EEG in localizing seizure onset in patients with dual seizure foci.

  14. [Possibilities of ultrasonic investigations in differentiation of a small-foci impairment of thyroid gland].

    Science.gov (United States)

    Reyti, A O; Vityuk, N V; Medvedev, V E; Starushok, I O

    2015-03-01

    The results of ultrasound investigation of microcarcinomas and nontumoral foci of thyroid gland up to 10 mm in diameter and malignant foci over 10 mm are presented. Ultrasound signs are depicted, in accordance to which a potentially malignant thyroid gland foci are delineated, what demands a morphological (cytological) verification conduction.

  15. Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation

    DEFF Research Database (Denmark)

    Vangsted, Annette; Gimsing, Peter; Klausen, Tobias W

    2007-01-01

    ) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C-allele of ERCC2 K751Q, the variant T-allele of XRCC3 T241M and the variant A...

  16. Multiple Myeloma

    Science.gov (United States)

    Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. These cells ... bones. No one knows the exact causes of multiple myeloma, but it is more common in older people ...

  17. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease

    Science.gov (United States)

    Coluzzi, Flaminia; Raffa, Robert B; Pergolizzi, Joseph; Rocco, Alessandra; Locarini, Pamela; Cenfra, Natalia; Cimino, Giuseppe; Mattia, Consalvo

    2015-01-01

    Context Myeloma bone disease (MBD) is a devastating complication of multiple myeloma that leads to severe pain. Objectives The aim of this study was to evaluate the efficacy and tolerability of tapentadol prolonged release (PR) in the management of patients with MBD suffering from moderate-to-severe cancer pain. Methods A 12-week prospective study was carried out in 25 opioid-naïve MBD patients. Patients initially received twice-daily doses of tapentadol PR 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity. The following parameters were recorded at weekly intervals for 4 weeks, and then at weeks 8 and 12: pain, opioid-related adverse effects, use of other analgesics, DN4 (Douleur Neuropathique 4) score. Quality of life (SF-36 [36-item short-form health survey]) was measured at baseline and at final evaluation. Results Of 25 patients, 22 completed the study. Pain intensity significantly decreased from baseline to all the week intervals (P<0.01). Quality of life significantly improved with respect to all SF-36 subscale parameters (P<0.01), and so did both the physical and mental status (P<0.01). Tapentadol PR significantly reduced DN4 mean value (P<0.01) and the number of patients with neuropathic component (DN4 ≥4) (P<0.01). After 8 weeks of treatment, all patients were negative for the DN4 score. Tapentadol PR was well tolerated, and the use of other analgesics was reduced during the study period. Conclusion Tapentadol PR started in doses of 100 mg/day was effective and well tolerated in opioid-naïve MBD patients with moderate-to-severe pain. Tapentadol PR can be considered a first-choice opioid in cancer patients suffering from mixed pain with a neuropathic component. PMID:26064064

  18. Mapping and assessment of epileptogenic foci using frequency-entropy templates

    Science.gov (United States)

    Ben-Jacob, Eshel; Doron, Itai; Gazit, Tomer; Rephaeli, Eden; Sagher, Oren; Towle, Vernon L.

    2007-11-01

    Much effort has been devoted to developing analysis methods of subdural electroencephalogram and depth electrode recordings of epileptic patients being evaluated for surgical resection. The general approach is to investigate the brain activity at different locations as recorded by the different electrodes in an attempt to localize the epileptogenic focus or foci. Currently, most of the methods are based on the notion that epileptogenic brain activity is associated with changes in synchronization and in complexity. Here we present a method that is based on the temporal dynamics combined with the spectral distribution of energy in terms of frequency-entropy (FE) templates. The FE templates are based upon maximum information partitioning into a set of frequency bands. The FE template is calculated by wavelet packet decomposition followed by an application of the best basis algorithm minimizing the entropy cost function. A comparison between two FE templates is performed by a special quantitative similarity measure according to the overlap in the partitioning into frequency bands and weighted by the bands’ entropy. For localization of the epileptogenic foci, the templates of each electrode during the interictal period are compared with a representative template evaluated from the ensemble of all electrodes during the ictal period. We suggest associating the locations that reveal high template similarity to the ictal template with the epileptogenic foci. To test the method and the underlying assumptions, we perform retrospective analysis of the recorded brain activity, from both grid and depth electrodes, from 11 patients suffering from medically intractable epilepsy. Application of the ictal-interictal FE template similarity analysis revealed regions in the epileptic brain in which the interictal characteristics are highly similar to those of the ictal period. To asses the foci we compared the interictal templates of the different electrodes to each other, forming

  19. Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Sakai, Eiji; Morioka, Takamitsu; Yamada, Eiji; Ohkubo, Hidenori; Higurashi, Takuma; Hosono, Kunihiro; Endo, Hiroki; Takahashi, Hirokazu; Takamatsu, Reika; Cui, Changxu; Shiozawa, Manabu; Akaike, Makoto; Samura, Hironori; Nishimaki, Tadashi; Nakajima, Atsushi; Yoshimi, Naoki

    2012-01-01

    In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm(2) . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis. © 2011 Japanese Cancer Association.

  20. [Incidence and imaging characteristics of skeletal metastases detected by bone scintigraphy in lung cancer patients].

    Science.gov (United States)

    Jauković, Ljiljana; Ajdinović, Boris; Janković, Zoran; Dugonjić, Sanja

    2006-12-01

    Detection of metastatic bone disease by skeletal scintigraphy is a classical application of nuclear medicine in cancer patients. Detection of bone metastases in patients with lung cancer is necessary for an appropriate treatment modality. The aim of this study was to report the frequency and imaging characteristics of bone metastases detected by bone scintigraphy (BS) using technetium-99m phosphonates in patients with lung cancer. We retrospectively analyzed a total of one hundred patients (78 males and 22 females), mean age of 63.3 years, with the diagnosis of lung cancer, who underwent BS during a three-year-period (2003-2005). Scintiscans were classified as positive, negative and suspicious with regard to the presence of bone metastases. The incidence of positive, negative and suspicious findings were 57%. 32% and 11%, respectively. Out of 57 patients with bone metastases, 51 had multiple asymmetric foci of increased tracer activity localized in the ribs, spine, extremities, pelvis, sternum, scapula and skull in 72%, 54%, 49%, 37%, 12%, 9% and 5% of scans, respectively. BS revealed solitary metastases in 6 of the patients. The lesions were located in the lower limbs in three patients and in the upper limbs, pelvis and sternum in the remaining three patients. Bone scintigraphy plays a significant role in staging and selecting of patients for curative lung surgery. Due to the fact that metastatic involvment of the extremities was frequently shown, our study suggests that systematic inclusion of the limbs in BS acquisition should be obligatory.

  1. Influence of Different Diets on Development of DMH-Induced Aberrant Crypt Foci and Colon Tumor Incidence in Wistar Rats

    DEFF Research Database (Denmark)

    Kristiansen, E.; Thorup, I.; Meyer, Otto A.

    1995-01-01

    The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACI;). Male Wistar rats were initiated with oral noses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once.......05) in the total number of ACF and number of small and medium ACF was observed. The values of large and extra-large foci reflected the same effect of diets on ACF. The results indicate that tumors in the group fed the diet high in refined carbohydrates were more prominent and occurred with a higher incidence....... However, the difference is based on few tumors and is not statistically significant. Our results do not show that the number of ACF and crypt multiplicity are conclusively predictive for tumor outcome with the present protocol, which did not include parameters to differentiate between ACF at the cellular...

  2. Dose-intensified bendamustine followed by autologous peripheral blood stem cell support in relapsed and refractory multiple myeloma with impaired bone marrow function.

    Science.gov (United States)

    Breitkreutz, Iris; Becker, Natalia; Benner, Axel; Kosely, Florentina; Heining, Christoph; Hillengass, Jens; Egerer, Gerlinde; Ho, Anthony D; Goldschmidt, Hartmut; Raab, Marc S

    2016-12-01

    Therapeutic options in heavily pretreated relapsed/refractory multiple myeloma patients are often very limited because of impaired bone marrow function. Bendamustine is effective in multiple myeloma and has a favourable toxicity profile. We hypothesized that dose-intensified bendamustine (180 mg/m(2) , day 1 and 2) followed by autologous blood stem cell support (ASCS) would improve bone marrow function with low post-transplant toxicity in patients with severely impaired haematopoiesis. We analyzed 28 consecutive myeloma patients, with a median of three prior lines of therapy (range 2-7), who had relapsed from the last treatment with very limited bone marrow function and were therefore ineligible for conventional chemotherapy, novel agents or trial enrolment. Dose-intensified bendamustine with ASCS improved haematopoiesis as reflected by increased platelet counts (median 40/nl vs 94/nl, p = 0.0004) and white blood cell counts (3.0/nl vs 4.8/nl, p = 0.02) at day +100. The median time until engraftment of platelets (>50/nl) was 11 days (0-24 days) and of white cell counts (>1.0/nl) 0 days (0-24 days). At least, a minimal response was achieved in 36% of patients. The disease stabilization rate was 50% while the median progression-free survival rate was limited to 2.14 months. Most importantly, patients were once again eligible for alternative treatments including enrolment into clinical trials. We conclude that dose-intensified bendamustine followed by ASCS is safe and feasible for multiple myeloma patients with very limited bone marrow reserve. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. miR-29b negatively regulates human osteoclastic cell differentiation and function: implications for the treatment of multiple myeloma-related bone disease.

    Science.gov (United States)

    Rossi, Marco; Pitari, Maria Rita; Amodio, Nicola; Di Martino, Maria Teresa; Conforti, Francesco; Leone, Emanuela; Botta, Cirino; Paolino, Francesco Maria; Del Giudice, Teresa; Iuliano, Eleonora; Caraglia, Michele; Ferrarini, Manlio; Giordano, Antonio; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2013-07-01

    Skeletal homeostasis relies upon a fine tuning of osteoclast (OCL)-mediated bone resorption and osteoblast (OBL)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease (BD). Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells, significantly impairs tartrate acid phosphatase (TRAcP) expression, lacunae generation, and collagen degradation, which are relevant hallmarks of OCL activity. Accordingly, expression of cathepsin K and metalloproteinase 9 (MMP9) as well as actin ring rearrangement were impaired in the presence of miR-29b. Moreover, we found that canonical targets C-FOS and metalloproteinase 2 are suppressed by constitutive miR-29b expression which also downregulated the master OCL transcription factor, NAFTc-1. Overall, these data indicate that enforced expression of miR-29b impairs OCL differentiation and overcomes OCL activation triggered by MM cells, providing a rationale for miR-29b-based treatment of MM-related BD.

  4. Detecting and localizing the foci in human epileptic seizures

    CERN Document Server

    Ben-Jacob, E; Pomyalov, A; Procaccia, I; Towle, V L; Ben-Jacob, Eshel; Boccaletti, Stefano; Pomyalov, Anna; Procaccia, Itamar; Towle, Vernon L.

    2007-01-01

    We consider the electrical signals recorded from a subdural ECoG grid of electrodes placed on the pial surface of the brain for chronic evaluation of epileptic patients before surgical resection. A simple and computationally fast method to analyze the inter-ictal phase synchrony between such electrodes is introduced and developed with the aim of detecting and localizing the foci of the epileptic events. We evaluate the method by comparing the results of surgery to the localization predicted here. We find an indication of good correspondence between the success or failure in the surgery and the agreement between our identification and the regions actually operated on.

  5. Electrical stimulation for epilepsy: stimulation of hippocampal foci.

    Science.gov (United States)

    Velasco, F; Velasco, M; Velasco, A L; Menez, D; Rocha, L

    2001-01-01

    Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

  6. Differential gene expression in CD45 cells at para-aortic foci stage of chicken haematopoiesis.

    Science.gov (United States)

    Säynäjäkangas, R; Uchida, T; Vainio, O

    2009-09-01

    Para-aortic foci of chicken embryos at 6-7 days of development are considered to provide a microenvironment for haematopoietic stem cell proliferation and initial differentiation similar to that of fetal liver in mammals. Here, we have investigated the genes involved in this process by constructing and analysing a subtractive cDNA library from CD45(+) cells in para-aortic region. Among 394 analysed clones 99 distinct genes were identified by sequence homology search. Classification of the identified genes according to biological processes revealed that innate immunity-related genes are highly expressed at this stage. This can be explained by the presence of yolk sac-derived macrophages in the original tissue sample but also by the indiscriminate expression of multiple lineage-specific genes in haematopoietic stem cells and primitive progenitors. Differentially expressed genes related to transcription, signalling and lymphocyte functions are potential candidates involved in lineage commitment.

  7. Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito, Davide, E-mail: davide.atena@tiscalinet.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Besostri, Valeria, E-mail: valeriabesostri@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Bonaffini, Pietro Andrea, E-mail: pa.bonaffini@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Rossini, Fausto, E-mail: valeriabesostri@hotmail.it [Department of Hematology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Di Lelio, Alessandro, E-mail: valebeso@libero.it [Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Sironi, Sandro, E-mail: sandrosironi@libero.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy)

    2013-12-01

    Purpose: To assess the role of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of patients with suspicion of multiple myeloma (MM). Materials and methods: A total of 138 patients (76 male and 62 female; mean age 63.5 years, range 50–81 years), with early MM, underwent WBLDCT protocol study, performed on 16-slice scanner (Brilliance, Philips Medical System, Eindhoven, The Netherlands): tube voltage 120 kV; tube current time product 40 mAs. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done by using multiplanar reformatted images. The overall dose delivered to each patient was 4.2 mSv. Every patient gave personal informed consent, as required by our institution guidelines. Results: The diagnosis was established either by histopathology or imaging follow-up (size increase of over a period time). In all 138 patients, image resolution was diagnostic, enabling correct classification of multiple myeloma patients. WBLDCT showed a total of 328 pathologic bone findings in 81/138 patients. CT scanning resulted in complete evaluation of the bone lesions in these areas of the skeleton: skull (42), humerus (15), femur (20), ribs (7), scapulae (13), pelvis (35), clavicle (13), sternum (10), cervical (39), dorsal (65), lombar (48) and sacral rachis (21). In 40/81 bone involvement detected by CT was the only CRAB criterion present. Furthermore, WBLDCT demonstrated pleuro-pulmonary lesions in 20 patients (11 infective, 9 as MM localizations) and 1 renal neoplasia. Conclusion: WBLDCT, detecting bone marrow localizations and demonstrating extra-osseous findings, with a fast scanning time and high resolution images, is a reliable imaging-based tool for a proper management of MM patients.

  8. Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    D.A. Schettini

    2005-12-01

    Full Text Available The aim of the present study was to evaluate the impact of a multiple dose regimen of a liposomal formulation of meglumine antimoniate (LMA on the pharmacokinetics of antimony in the bone marrow of dogs with visceral leishmaniasis and on the ability of LMA to eliminate parasites from this tissue. Dogs naturally infected with Leishmania chagasi received 4 intravenous doses of either LMA (6.5 mg antimony/kg body weight, N = 9, or empty liposomes (at the same lipid dose as LMA, N = 9 at 4-day intervals. A third group of animals was untreated (N = 8. Before each administration and at different times after treatment, bone marrow was obtained and analyzed for antimony level (LMA group by electrothermal atomic absorption spectrometry, and for the presence of Leishmania parasites (all groups. There was a significant increase of antimony concentration from 0.76 µg/kg wet organ (4 days after the first dose to 2.07 µg/kg (4 days after the fourth dose and a half-life of 4 days for antimony elimination from the bone marrow. Treatment with LMA significantly reduced the number of dogs positive for parasites (with at least one amastigote per 1000 host cells compared to controls (positive dogs 30 days after treatment: 0 of 9 in the LMA group, 3 of 9 in the group treated with empty liposomes and 3 of 8 in the untreated group. However, complete elimination of parasites was not achieved. In conclusion, the present study showed that multiple dose treatment with LMA was effective in improving antimony levels in the bone marrow of dogs with visceral leishmaniasis and in reducing the number of positive animals, even though it was not sufficient to achieve complete elimination of parasites.

  9. RNA/MBNL1-containing foci in myoblast nuclei from patients affected by myotonic dystrophy type 2: an immunocytochemical study

    Directory of Open Access Journals (Sweden)

    F. Perdoni

    2009-09-01

    Full Text Available Myotonic dystrophy type 2 (DM2 is a dominantly inherited autosomal disease with multi-systemic clinical features and it is caused by expansion of a CCTG tetranucleotide repeat in the first intron of the zinc finger protein 9 (ZNF9 gene in 3q21.The expanded-CCUG-containing transcripts are retained in the cell nucleus and accumulate in the form of focal aggregates which specifically sequester the muscleblind-like 1 (MBNL1 protein, a RNA binding factor involved in the regulation of alternative splicing. The structural organization and composition of the foci are still incompletely known. In this study, the nuclear foci occurring in cultured myoblasts from DM2 patients were characterised at fluorescence and transmission electron microscopy by using a panel of antibodies recognizing transcription and processing factors of pre-mRNAs. MBNL1 proved to co-locate in the nuclear foci with snRNPs and hnRNPs, whereas no co-location was observed with RNA polymerase II, the non-RNP splicing factor SC35, the cleavage factor CStF and the PML protein. At electron microscopy the MBNL1-containing nuclear foci appeared as roundish domains showing a rather homogeneous structure and proved to contain snRNPs and hnRNPs. The sequestration of splicing factors involved in early phases of pre-mRNA processing supports the hypothesis of a general alteration in the maturation of several mRNAs, which could lead to the multiple pathological dysfunctions observed in dystrophic patients.

  10. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Ambrosini Valentina

    2007-06-01

    Full Text Available Abstract Background Multiple Myeloma (MM is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS, Magnetic resonance (MR and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40% had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20% had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40% had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042. Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8. Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

  11. Surveillance of endemic foci of tick-borne encephalitis in Finland 1995-2013: evidence of emergence of new foci.

    Science.gov (United States)

    Tonteri, Elina; Kurkela, Satu; Timonen, Suvi; Manni, Tytti; Vuorinen, Tytti; Kuusi, Markku; Vapalahti, Olli

    2015-01-01

    The geographical risk areas for tick-borne encephalitis (TBE) in Finland remained the same until the beginning of the 21st century, but a considerable geographical expansion has been observed in the past 10 years. In order to support public health measures, the present study describes the number of laboratory-confirmed TBE cases and laboratory tests conducted and the associated trends by hospital district, with a particular emphasis on the suspected geographical risk areas. An additional investigation was conducted on 1,957 clinical serum samples throughout the country taken from patients with neurological symptoms to screen for undiagnosed TBE cases. This study identified new TBE foci in Finland, reflecting the spread of the disease into new areas. Even in the most endemic municipalities, transmission of TBE to humans occurred in very specific and often small foci. The number of antibody tests for TBE virus more than doubled (an increase by 105%) between 2007 and 2013. Analysis of the number of tests also revealed areas in which the awareness of clinicians may be suboptimal at present. However, it appears that underdiagnosis of neuroinvasive TBE is not common.

  12. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  13. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    Directory of Open Access Journals (Sweden)

    Dyondi D

    2012-12-01

    Full Text Available Deepti Dyondi,1 Thomas J Webster,2 Rinti Banerjee11Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India; 2Nanomedicine Laboratories, Division of Engineering and Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF, and bone morphogenetic protein 7 (BMP7 were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.Keywords: bone tissue engineering, bone morphogenetic protein 7 (BMP7, basic fibroblast growth factor (bFGF, hydrogel, nanoparticles, osteoblasts

  14. Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease

    DEFF Research Database (Denmark)

    Sezer, Orhan; Beksac, Meral; Hajek, Roman

    2017-01-01

    This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycl...

  15. On the distribution of trace element concentrations in multiple bone elements in 10 Danish medieval and post-medieval individuals.

    Science.gov (United States)

    Lund Rasmussen, Kaare; Skytte, Lilian; D'imporzano, Paolo; Orla Thomsen, Per; Søvsø, Morten; Lier Boldsen, Jesper

    2017-01-01

    The differences in trace element concentrations among 19 different bone elements procured from 10 archaeologically derived human skeletons have been investigated. The 10 individuals are dated archaeologically and some by radiocarbon dating to the medieval and post-medieval period, an interval from ca. AD 1150 to ca. AD 1810. This study is relevant for two reasons. First, most archaeometric studies analyze only one bone sample from each individual; so to what degree are the bones in the human body equal in trace element chemistry? Second, differences in turnover time of the bone elements makes the cortical tissues record the trace element concentrations in equilibrium with the blood stream over a longer time earlier in life than the trabecular. Therefore, any differences in trace element concentrations between the bone elements can yield what can be termed a chemical life history of the individual, revealing changes in diet, provenance, or medication throughout life. Thorough decontamination and strict exclusion of non-viable data has secured a dataset of high quality. The measurements were carried out using Inductively Coupled Plasma Mass Spectrometry (for Fe, Mn, Al, Ca, Mg, Na, Ba, Sr, Zn, Pb and As) and Cold Vapor Atomic Absorption Spectroscopy (for Hg) on ca. 20 mg samples. Twelve major and trace elements have been measured on 19 bone elements from 10 different individuals interred at five cemeteries widely distributed in medieval and renaissance Denmark. The ranges of the concentrations of elements were: Na (2240-5660 µg g(-1) ), Mg (440-2490 µg g(-1) ), Al (9-2030 µg g(-1) ), Ca (22-36 wt. %), Mn (5-11450 µg g(-1) ), Fe (32-41850 µg g(-1) ), Zn (69-2610 µg g(-1) ), As (0.4-120 µg g(-1) ), Sr (101-815 µg g(-1) ), Ba (8-880 µg g(-1) ), Hg (7-78730 ng g(-1) ), and Pb (0.8-426 µg g(-1) ). It is found that excess As is mainly of diagenetic origin. The results support that Ba and Sr concentrations are effective provenance or dietary indicators

  16. Ultramicrostructure and clinical implications of satellite foci in front of the head of pterygium

    Institute of Scientific and Technical Information of China (English)

    LIU Haixia; XIANG Nan; ZHOU Xiongwu; HU Weikun; LI Guigang; ZHANG Hong

    2007-01-01

    In our previous studies,grey satellite foci were found in the front of heads of pterygia.This research was designed to investigate the ultramicrostructure and clinical implications of these satellite foci.The satellite foci were observed and counted under slit lamp biomicroscope.The patients with eye pterygia were divided into groups in terms of occupation,sex,age,length of history,grade of congestion,and size of the heads.The SPSS 13.0 software was used for statistical analysis.The cap areas and satellite foci were ultramicrostructurally examined.Among the total 62 eyes with pterygium,satellite foci were found in 34.The overall incidence of satellite foci was 54.8%.There were no significant differences in incidence among the subjects of different sex,age,and length of history.There were significant differences in incidence among the patients of different occupation,grades of congestion,and size of heads.Higher grades of congestion,outdoor occupations and larger pterygium heads were associated with higher incidence of satellite foci.High grades of congestion and bigger heads were also correlated with the number of satellite foci.Length of history bore no correlation with number of satellite foci.Histologically,the components of the cap areas and the foci were identical,with both consisting of mass of active fibroblasts.The activated fibroblasts existed in the natural tissue planes between Bowman's layer and basal cell layer.The fibroblasts in the satellite foci and the cap areas of a pterygium show some features of tumor cells and may play a vital role in the development and progression of a pterygium.The presence and amount of satellite foci around a pterygium can be used as an indicator for the speed of its growth.

  17. A novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant antimyeloma activity.

    Science.gov (United States)

    Eda, H; Santo, L; Cirstea, D D; Yee, A J; Scullen, T A; Nemani, N; Mishima, Y; Waterman, P R; Arastu-Kapur, S; Evans, E; Singh, J; Kirk, C J; Westlin, W F; Raje, N S

    2014-09-01

    Bruton's tyrosine kinase (Btk) modulates B-cell development and activation and has an important role in antibody production. Interestingly, Btk may also affect human osteoclast (OC) function; however, the mechanism was unknown. Here we studied a potent and specific Btk inhibitor, CC-292, in multiple myeloma (MM). In this report, we demonstrate that, although CC-292 increased OC differentiation, it inhibited OC function via inhibition of c-Src, Pyk2 and cortactin, all involved in OC-sealing zone formation. As CC-292 did not show potent in vitro anti-MM activity, we next evaluated it in combination with the proteasome inhibitor, carfilzomib. We first studied the effect of carfilzomib on OC. Carfilzomib did not have an impact on OC-sealing zone formation but significantly inhibited OC differentiation. CC-292 combined with carfilzomib inhibited both sealing zone formation and OC differentiation, resulting in more profound inhibition of OC function than carfilzomib alone. Moreover, the combination treatment in an in vivo MM mouse model inhibited tumor burden compared with CC-292 alone; it also increased bone volume compared with carfilzomib alone. These results suggest that CC-292 combined with carfilzomib augments the inhibitory effects against OC within the bone microenvironment and has promising therapeutic potential for the treatment of MM and related bone disease.

  18. The mathematics of mosaic analysis. II. Formulae for interacting foci.

    Science.gov (United States)

    Wyman, R J; Salkoff, L

    1982-04-01

    Mosaic fate mapping requires first a measurement of the frequency of separation (by genotype) of two structures and then a conversion of this frequency of separation to distance (WYMAN and THOMAS 1982). If the genotype of two structures is visible, the frequency of separation (sturt distance) may be directly obtained. If the genotype is not visible (e.g., for behavioral foci) then the frequency of separation (sturt distance) itself must be calculated. The formulae introduced by HOTTA and BENZER (1972) for calculating frequency of separation are appropriate only for a set of mosaics in which each fly has half normal and half mutant tissue. Using these formulae for a set of mosaics with a different fraction of mutant tissue can give enormously incorrect results.--In this paper we use intuitive lines of reasoning to obtain simple formulae for frequencies of separation that are algebraically equal to the more elaborate HOTTA and BENZER (1972) formulae.--We show that when calculating sturt distances, data from a collection of mosaics with a range of malenesses, even if the average maleness is 1/2, cannot be lumped together. We prove that applying any formula appropriate for m = 1/2 to a set of mosaics all of maleness m, and then to a set of maleness 1-m, and then averaging the two results, does give the correct value for sturt distances. In this way all the mapping distances may be obtained.--Another method for locating foci is called "contour mapping". We show that the currently available contour formulae are inaccurate. We suggest that contour maps be drawn using the accurate sturt distances.

  19. Analysis of Clinical Treatment of Multiple Injuries of Bone and Joint%多发性骨与关节损伤的临床治疗分析

    Institute of Scientific and Technical Information of China (English)

    王瑞阳

    2015-01-01

    目的:对多发性骨于关节损伤的临床治疗进行探讨分析,了解多发性骨与关节损伤的特点和治疗方法。方法此次根据我院接收的100例骨与关节损伤患者来进行研究分析,根据其临床治疗资料进行回顾。结果经过治疗共有5例患者死亡,主要是失血休克、脂肪栓塞综合征、急性肾衰的导致的,临床死亡率5%,后期有6例接收二次手术,4例漏诊,有68例完全康复,愈合延迟8例,2例截肢,4例漏诊,7例膝关节功能减退。结论多发性骨和关节损伤在院前急救时需要提供比较好的处理,为院内急救提供基础,对该类患者的漏诊原因进行分析,提升诊断准确率,引导患者的术后功能锻炼,提升康复几率。%Objective To analyze the clinical treatment of multiple bone to joint injury, understand the characteristics and treatment of multiple injuries of bone and joint.Methods the according to our hospital received 100 patients with bone and joint injuries to study and analyze, review according to the clinical treatment data.Resultsafter treatment for a total of 5 patients died, mainly hemorrhagic shock, fat embolism syndrome, acute renal failure causes, clinical mortality was 5%, and later 6 cases received two times operation, 4 cases of misdiagnosis, 68 cases recovered completely, 8 cases of delayed healing, 2 cases of amputation, 4 cases were missed, 7 cases of knee joint dysfunction.Conclusion multiple bone and joint injuries need to provide better handling in pre hospital ifrst aid, and provides a basis for the treatment in hospital, the causes of misdiagnosis of the patients analyzed, improve the accuracy rate of diagnosis, patients with postoperative functional exercise guidance, enhance the chance of recovery.

  20. Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development.

    Science.gov (United States)

    Mangiavini, Laura; Merceron, Christophe; Araldi, Elisa; Khatri, Richa; Gerard-O'Riley, Rita; Wilson, Tremika LeShan; Rankin, Erinn B; Giaccia, Amato J; Schipani, Ernestina

    2014-09-01

    Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements.

  1. Toll-like receptor (TLR-1/2 triggering of multiple myeloma cells modulates their adhesion to bone marrow stromal cells and enhances bortezomib-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Jahangir Abdi

    Full Text Available In multiple myeloma (MM, the malignant plasma cells usually localize to the bone marrow where they develop drug resistance due to adhesion to stromal cells and various environmental signals. Hence, modulation of this interaction is expected to influence drug sensitivity of MM cells. Toll-like receptor (TLR ligands have displayed heterogeneous effects on B-cell malignancies and also on MM cells in a few recent studies, but effects on adhesion and drug sensitivity of myeloma cells in the context of bone marrow stromal cells (BMSCs have never been investigated. In the present study, we explored the modulatory effects of TLR1/2 ligand (Pam3CSK4 on adhesion of human myeloma cells to BMSCs. It is shown that TLR1/2 triggering has opposite effects in different HMCLs on their adhesion to BMSCs. Fravel, L363, UM-6, UM-9 and U266 showed increased adhesion to BMSC in parallel with an increased surface expression of integrin molecules α4 and αVβ3. OPM-1, OPM-2 and NCI-H929 showed a dose-dependent decrease in adhesion upon TLR activation following a downregulation of β7 integrin expression. Importantly, TLR1/2 triggering increased cytotoxic and apoptotic effects of bortezomib in myeloma cells independent of the effect on stromal cell adhesion. Moreover, the apoptosis-enhancing effect of Pam3CSK4 paralleled induction of cleaved caspase-3 protein in FACS analysis suggesting a caspase-dependent mechanism. Our findings uncover a novel role of TLR activation in MM cells in the context of bone marrow microenvironment. Stimulation of TLR1/2 bypasses the protective shield of BMSCs and may be an interesting strategy to enhance drug sensitivity of multiple myeloma cells.

  2. Effective elastic properties of a composite containing multiple types of anisotropic ellipsoidal inclusions, with application to the attachment of tendon to bone

    Science.gov (United States)

    Saadat, Fatemeh; Birman, Victor; Thomopoulos, Stavros; Genin, Guy M.

    2015-09-01

    Estimates of the effective stiffness of a composite containing multiple types of inclusions are needed for the design and study of a range of material systems in engineering and physiology. While excellent estimates and tight bounds exist for composite systems containing specific classes and distributions of identical inclusions, these are not easily generalized to systems with multiple types of inclusions. The best estimate available for a composite containing multiple classes of inclusions arises from the Kanaun-Jeulin approach. However, this method is analogous to a generalized Benveniste approach, and therefore suffers from the same limitations: while excellent for low volume fractions of inclusions, the Kanaun-Jeullin and Benveniste estimates liebelow three-point bounds at higher volume fractions. Here, we present an estimate for composites containing multiple classes of aligned ellipsoidal inclusions that lies within known three-point bounds at relatively higher volume fractions of inclusions and that is applicable to many engineering and biological composites. The approach involves replacing the averaged strains used in the Kanaun-Jeulin method with an effective strain measure. We demonstrate application of the constitutive model to the graded tissue system at the attachment of tendon to bone.

  3. Multiple bone metastases detected on 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography in a breast cancer patient: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Zeki Dostbil

    2012-09-01

    Full Text Available Bone scintigraphy has been widely used to assess skeletal metastasis in patients with breast cancer. 18F-FDGPET/CT is another imaging modality that has gained previously wide use to determine metastasis based on increased glucose metabolism in malignant cells. Generally, these two modalities give similar results in evaluation of bone metastasis of breast cancer. In this breast cancer case, 99mTc-MDP bone scintigraphy showed normal findings in regards to skeletal metastasis while 18FFDG-PET/CT, contrast-enhanced CT and MRI revealed multiple metastatic focuses. J Clin Exp Invest 2012; 3 (3: 426-429Key words: 18F-fluorodeoxyglucose, bone metastasis, bone scintigraphy, positron emission tomography

  4. Gracile bone dysplasias

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, Kazimierz [Department of Medical Imaging, The Children' s Hospital at Westmead, Locked Bag 4001, Westmead 2145, NSW (Australia); Masel, John [Department of Radiology, Royal Children' s Hospital, Brisbane (Australia); Sillence, David O. [Department of Paediatrics and Child Health, The University of Sydney (Australia); Arbuckle, Susan [Department of Anatomical Pathology, The Children' s Hospital at Westmead, NSW (Australia); Juttnerova, Vera [Oddeleni Lekarske Genetiky, Hradec Kralove (Czech Republic)

    2002-09-01

    Gracile bone dysplasias constitute a group of disorders characterised by extremely slender bones with or without fractures. We report four newborns, two of whom showed multiple fractures. Two babies had osteocraniostenosis and one had features of oligohydramnios sequence. The diagnosis in the fourth newborn, which showed thin long bones and clavicles and extremely thin, poorly ossified ribs, is uncertain. Exact diagnosis of a gracile bone dysplasia is important for genetic counselling and medico-legal reasons. (orig.)

  5. Retrospective Analysis of Multiple Bone and Joint Injuries%多发性骨与关节损伤病例回顾分析

    Institute of Scientific and Technical Information of China (English)

    颜滨

    2014-01-01

    Objective Analysis of multiple injuries of bone and joint were diagnosed by clinical features, diagnosis and treatment of purpose.Methods Multiple injuries of bone and joint and related mat ers needing at ention. Clinical data of our hospital has treated 100 cases of bone and joint injury were analyzed. Results The treatment results showed, 5 patients died, the cause of death was hemor hagic shock, fat embolism syndrome (FES) and acute renal failure (ARF), treatment rate 5%, later, need a two operation in patients with 6 cases (6%), the occur ence of missed 4 cases (4%), the function of knee joint in 7 cases (7%), do amputation operation was 2 cases (2%), delayed wound healing in 8 cases (8%), 68 cases recovered completely (68%). Conclusion First aid at ention of multiple injuries of bone and joint pre hospital, strengthen the emergency personnel and medical staf training, analysis of the multiple injuries of bone and joint the cause of missed diagnosis, reduce misdiagnosis, adhering to the operation principle of treatment, to actively guide the postoperative functional exercise. Improve patients recovery rate.%目的:通过分析讨论多发性骨与关节损伤病例,研究多发性骨与关节损伤的临床特点、诊治方法及相关注意事项。方法对我院近期收治的100例骨与关节损伤患者的临床治疗资料进行分析。结果治疗结果显示,有5例患者死亡,死亡原因分别是失血性休克、脂肪栓塞综合征(FES)以及急性肾功能衰竭(ARF),死亡率5%,后期治疗,需要二次手术的患者有6例(6%),发生漏诊的患者有4例(4%),膝关节功能下降7例(7%),做截肢手术的有2例(2%),愈合延迟8例(8%),完全康复68例(68%)。结论重视多发性骨与关节损伤的院前急救,强化对急救人员以及门诊医护人员的培训,分析多发性骨与关节损伤漏诊原因,减少漏诊、坚持手术治疗原则,要积极引导患者术后功能锻炼。提高患者的康复率。

  6. Role of {sup 18}F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina; Farsad, Mohsen; Castellucci, Paolo; Fanti, Stefano [Policlinico S.Orsola-Malpighi, UO Medicina Nucleare, Bologna (Italy); Zamagni, Elena; Tosi, Patrizia; Cangini, Delia; Cavo, Michele [Policlinico S.Orsola-Malpighi, Istituto di Ematologia, Bologna (Italy); Salizzoni, Eugenio; Canini, Romeo [Policlinico S.Orsola-Malpighi, Istituto di Radiologia, Bologna (Italy)

    2006-05-15

    Purpose Multiple myeloma (MM) is a malignant B cell and plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. The aim of this study was to compare whole-body X-ray (WBXR), MRI and {sup 18}F-FDG PET/CT in patients with MM. Methods The study population comprised 28 newly diagnosed MM patients. Findings of {sup 18}F-FDG PET/CT were compared with those of WBXR and MRI with regard to the number and site of lesions detected. Results Comparing 18F-FDG PET/CT and WBXR, it was found that in 16/28 pts (57%) {sup 18}F-FDG PET/CT detected more lesions, all of which were located in the skeleton. Nine of these 16 patients had a completely negative WBXR survey. In 12/28 pts (43%) the two methods yielded equivalent findings. Comparing {sup 18}F-FDG PET/CT and MRI, it was found that in 7/28 pts (25%), {sup 18}F-FDG PET/CT detected more lytic bone lesions, all of which were located outside the field of view of MRI (bone lesions in six cases and a soft tissue lesion in one). In 14/28 pts (50%), {sup 18}F-FDG PET/CT and MRI detected the same number of lesions in the spine and pelvis, while in 7/28 pts (25%) MRI detected an infiltrative pattern in the spine whereas {sup 18}F-FDG PET/CT was negative. Conclusion {sup 18}F-FDG PET/CT appears to be more sensitive than WBXR for the detection of small lytic bone lesions, whereas it has the same sensitivity as MRI in detecting bone disease of the spine and pelvis. On the other hand, MRI may be superior to 18F-FDG PET/CT in diagnosing an infiltrative pattern in the spine. Therefore, careful evaluation of MM bone disease at diagnosis should include both MRI of the spine and {sup 18}F-FDG PET/CT.

  7. Findings of skin and bones in mastocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Rohner, H.G.; Bartl, R.; Koischwitz, D.; Rodermund, O.E.

    1982-12-01

    The syndrome of mastocytosis can include isolated urticaria pigmentosa, systemic mastocytosis, or the extremely rare form of mast cell leucemia. Our investigations of many patients have shown more frequently than earlier suspected, that the mastocytosis is a systemic disease. The frequency of attacked bone marrow is noteworthy. Because of the inflammatory granulomatous manifestation in bone marrow, considerations of the pathogenesis of an immune and reactive event are taken into account. The mast cell granulomas are mostly found in the endosteal region, which is the reason for frequently occurring bone lesions (half of all patients show bone lesions). The bone changes can develop generalized (osteoporosis-osteosclerosis) or localized (osteolytic-osteosclerotic foci). In clinical work bone biopsies and skeletal radiology are supplementing each other: bone biopsy and skin biopsy give the first diagnosis of mastocytosis and reveal the systemic disease; X-ray pictures give information of shape and dimension of the induced osteopathy.

  8. [Evolution of hyperplastic foci in the rat liver induced by diethylnitrosamine].

    Science.gov (United States)

    Gel'shteĭn, V I; Chipysheva, T A; Bannikov, G A

    1984-01-01

    The immunohistochemical localization of ligandin (L), A-protein (A) and alpha-fetoprotein (AFP) was studied in the liver of rats treated intraperitoneally with diethylnitrosamine (DENA). In early foci of altered cells there was a consecutive change in the content of antigens. The uniform content of L and A in these foci changed for the uniform content of only one marker. Late foci of altered hepatocytes were characterized by a heterogeneous distribution of the markers. 12-14 weeks after the treatment the neoplastic nodules with different antigenic phenotypes dependent on the morphological structure were detected. Cells in neoplastic nodules were uniform as to the marker content. Alpha-fetoprotein was unavailable in foci of altered cells and in neoplastic nodules either. It is concluded that evolution of most of foci follows the way of postnatal maturation similar to that in the normal liver and neoplastic nodules represent a side branch of differentiation blocked at different stages.

  9. Primary investigation of dose-effect relationship of 153Sm-EDTMP in treating multiple bone metastases%153Sm-EDTMP治疗多发骨转移瘤的剂量效应关系初步观察

    Institute of Scientific and Technical Information of China (English)

    Wei Fan; Lixin Chen; Xiaowei Liu; Qiang Tang; Shengfang Zhi; Zongyuan Zeng

    2007-01-01

    Objective: To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo (MC) EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer, and investigate the relationship between the focus absorption dose and painkilling effect of 153Sm-EDTMP. Methods: Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade Ⅳ bone pain were treated with radionuclide internal irradiation of 153Sm-EDTMP. The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation. The release of bone pain and the improvement of life quality were observed. Results: Bone pain of the patients was significantly alleviated to grade Ⅱ for 3-4 weeks after internal 153Sm-EDTMP irradiation. The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical. After injection of 0.65 × 37 MBq/kg 153Sm-EDTMP, the highest absorption dose in bone lesions was about 4.9-5.9 Gy, and the dose in the lesion margin was about 2.0 Gy. Using the highest dose as reference dose point, the relative absorption dose values of bone marrow, vertebra and sex organ near lesions were 0.48-1.1 Gy, 0.51-0.85 Gy, and 0.01-0.14 Gy, respectively. Conclusion: The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of 153Sm-EDTMP. The painkilling effect is limited and in accordance with clinical observation.

  10. Aberrant crypt foci as microscopic precursors of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Lei Cheng; Mao-De Lai

    2003-01-01

    Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), β-catenin, placental cadherin (P-cadherin),epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable in ACF Two hypotheses have been proposed.One is the "dysplasia ACF-adenoma-carcinoma sequence",the other is "heteroplastic ACF-adenoma-carcinoma sequence". The malignant potential of ACF, especially dyspiastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect "in vivo' ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC,and developing preventive procedures.

  11. Plague foci in Viet Nam: zoological and parasitological aspects.

    Science.gov (United States)

    Suntsov, V V; Huong, L T; Suntsova, N I; Gratz, N G

    1997-01-01

    Reported are the results of studies over the period 1989-94 on host-flea complexes in small mammals and their flea ectoparasites in and around a number of human settlements in Viet Nam in which human cases of plague had been found. Collections were also made in savanna and tropical forest areas within a 10-km radius of the settlements. The greatest numbers of small mammals, for the most part Rattus spp., and of the flea ectoparasite Xenopsylla cheopis were found in inhabited areas. X. cheopis was not found on any feral or sylvan mammal further than 0.6 km from settlements. A possible link between wild and commensal mammals may be provided by the flea Lentistivalius klossi, a specific parasite of squirrels and tree-shrews but also found in very small numbers on commensal rats. No zoonotic foci of plague were found in the immediate vicinity of the villages studied and it is most likely that plague persists in a commensal rat-X. cheopis cycle in and around human settlements in Viet Nam.

  12. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases.

    Science.gov (United States)

    Karussis, Dimitrios; Kassis, Ibrahim; Kurkalli, Basan Gowda S; Slavin, Shimon

    2008-02-15

    Bone marrow (BM) derived mesenchymal stem cells (MSCs) (non-hematopoietic, stromal cells) can differentiate under certain circumstances into cells from various neuronal and glial type lineages; they also exert immunomodulatory effects. For potential clinical applications, BM-MSCs offer significant practical advantages over other types of stem cells, since they can be obtained from the adult BM (the patient himself being the donor) and can be easily cultured and expanded posing in parallel a very low risk for development of malignancies. We have shown that BM-MSCs cultured with a cocktail of growth factors (containing FGF and BDNF) differentiate into neuronal/glial lineage cells with a predominance of cells expressing astrocytes' markers. BM-MSCs were effective in suppression of chronic EAE in mice and induced neuroprotection, preserving most of the axons in the CNS of successfully-treated animals. Histopathological studies revealed that MSCs could efficiently migrate into the CNS inflamed tissue (both when administered intravenously and intraventricularly) and differentiated into cells expressing neural-glial lineage markers. Our preclinical results indicate that bone marrow can provide a source of stem cells with a potential for migration into inflamed CNS tissue and differentiation into cells expressing neuronal and glial cell markers. Such an approach may provide a feasible and practical way for in situ immunomodulation, neuroprotection and possibly remyelination/regeneration in diseases like multiple sclerosis. We therefore developed a explorative protocol for the evaluation of this therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.

  13. Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin?

    Science.gov (United States)

    Marchica, Valentina; Accardi, Fabrizio; Storti, Paola; Mancini, Cristina; Martella, Eugenia; Dalla Palma, Benedetta; Bolzoni, Marina; Todoerti, Katia; Marcatti, Magda; Schifano, Chiara; Bonomini, Sabrina; Sammarelli, Gabriella; Neri, Antonino; Ponzoni, Maurilio; Aversa, Franco; Giuliani, Nicola

    2017-01-01

    The skin is a possible site of extramedullary localization in multiple myeloma (MM) patients; however, the mechanisms involved in this process are poorly understood. We describe the case of a refractory MM patient who developed a cutaneous localization under bortezomib treatment and we further expanded observations in other eight MM patients. We focused on the expression of genes involved in plasma cell skin homing, including CCR10, which was highly expressed. Moreover, we observed a lack of CXCR4 surface expression and the down-regulation of ICAM1/CD54 throughout the progression of the disease, suggesting a possible mechanism driving the escape of MM cells from the bone marrow into the skin.

  14. Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects

    Science.gov (United States)

    2013-04-29

    also suggests that the lymphatics play a critical role in fracture repair. With normal healing of tibial fracture, foci of ossification are...Effectiveness in segmental tibial defects in rats. Tissue Eng 12:489–497. Finkemeier CG. 2002. Bone-grafting and bone-graft substitutes. J Bone Joint...Vogelin E, Brekke JH, Jones NF. 2000. Heterotopic and orthotopic bone formation with a vascularized periosteal flap, a matrix and rh-BMP- 2 (bone

  15. The value of radionuclide bone imaging on monitoring chemotherapeutic effects of multiple myeloma%核素骨显像在多发性骨髓瘤疗效评价中的应用

    Institute of Scientific and Technical Information of China (English)

    Yongli Bai; Shuyao Zuo; Chao Ma; Xiaoting Su

    2008-01-01

    Objective: To investigate the value of radionuclide whole-body bone imaging on monitoring chemotherapeutic effects for multiple myeloma (MM). Methods: Sixty patients were included. Twenty nine cases received CTD (thalidomide 100-200 mg/d; cyclophosphamide 200-300 mg/m2·d, 1-4 days, every 4 weeks; and dexamethasone 20-40 rag/d, 1-4 days, every 4 weeks); Thirty cases received VAD (vincristine 0.4 mg/d, 1-4 days, every 4 weeks; adriamycin 10 rag/d, 1-4 days, ev-ery 4 weeks; dexamethasone 40 mg/d, 1-4 days, every 4 weeks). Radionuclide bone imagings were performed in all patients before chemotherapy, six months, twelve months and eighteen months after chemotherapy. The correlation of chemotherapeutic effects between CTD and VAD were analyzed. Results: One hundred and seventy nine bone lesions were visualized by bone scintigraphy before CTD treatment. Eighteen months after CTD chemotherapy, it was observed by bone scintigraphy that 39/179 (21.78%) lesions disappeared, 112/179 (62.57%)improved, and 28/179 (15.64%) had no change. One hundred and ninety one bone lesions were showed by bone imaging before VAD treatment, 36/191 (18.84%) lesions disappeared, eighteen months after chemotherapy, 103/191 (53.92%) improved, and 52/191 (27.22%) had no change. The significant difference was observed in locations of MM induced bone lesions treated with CTD (H = 8.23, P < 0.05) and VAD (H = 11.18, P < 0.05). A significant chemotherapeutic sensitivity in detecting MM induced lesions in ribs was found compared with other bone lesions. The chemotherapeutic effect of CTD was statistically significant than that of VAD (U = 2.17, P < 0.05). Conclusion: Radionuclide whole-body bone imaging has great value in monitoring chemotherapeutic effects for MM.

  16. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci.

    Science.gov (United States)

    Dion, Vincent; Kalck, Véronique; Seeber, Andrew; Schleker, Thomas; Gasser, Susan M

    2013-11-01

    The regulation of chromatin mobility in response to DNA damage is important for homologous recombination in yeast. Anchorage reduces rates of recombination, whereas increased chromatin mobility correlates with more efficient homology search. Here we tracked the mobility and localization of spontaneous S-phase lesions bound by Rad52, and find that these foci have reduced movement, unlike enzymatically induced double-strand breaks. Moreover, spontaneous repair foci are positioned in the nuclear core, abutting the nucleolus. We show that cohesin and nucleolar integrity constrain the mobility of these foci, consistent with the notion that spontaneous, S-phase damage is preferentially repaired from the sister chromatid.

  17. Bone Biopsy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging ... the limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided ...

  18. In-vehicle extremity injuries from improvised explosive devices: current and future foci.

    Science.gov (United States)

    Ramasamy, Arul; Masouros, Spyros D; Newell, Nicolas; Hill, Adam M; Proud, William G; Brown, Katherine A; Bull, Anthony M J; Clasper, Jon C

    2011-01-27

    The conflicts in Iraq and Afghanistan have been epitomized by the insurgents' use of the improvised explosive device against vehicle-borne security forces. These weapons, capable of causing multiple severely injured casualties in a single incident, pose the most prevalent single threat to Coalition troops operating in the region. Improvements in personal protection and medical care have resulted in increasing numbers of casualties surviving with complex lower limb injuries, often leading to long-term disability. Thus, there exists an urgent requirement to investigate and mitigate against the mechanism of extremity injury caused by these devices. This will necessitate an ontological approach, linking molecular, cellular and tissue interaction to physiological dysfunction. This can only be achieved via a collaborative approach between clinicians, natural scientists and engineers, combining physical and numerical modelling tools with clinical data from the battlefield. In this article, we compile existing knowledge on the effects of explosions on skeletal injury, review and critique relevant experimental and computational research related to lower limb injury and damage and propose research foci required to drive the development of future mitigation technologies.

  19. Gene network analysis of bone marrow mononuclear cells reveals activation of multiple kinase pathways in human systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Magdalene Nakou

    Full Text Available BACKGROUND: Gene profiling studies provide important information for key molecules relevant to a disease but are less informative of protein-protein interactions, post-translational modifications and regulation by targeted subcellular localization. Integration of genomic data and construction of functional gene networks may provide additional insights into complex diseases such as systemic lupus erythematosus (SLE. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed gene expression microarray data of bone marrow mononuclear cells (BMMCs from 20 SLE patients (11 with active disease and 10 controls. Gene networks were constructed using the bioinformatic tool Ingenuity Gene Network Analysis. In SLE patients, comparative analysis of BMMCs genes revealed a network with 19 central nodes as major gene regulators including ERK, JNK, and p38 MAP kinases, insulin, Ca(2+ and STAT3. Comparison between active versus inactive SLE identified 30 central nodes associated with immune response, protein synthesis, and post-transcriptional modification. A high degree of identity between networks in active SLE and non-Hodgkin's lymphoma (NHL patients was found, with overlapping central nodes including kinases (MAPK, ERK, JNK, PKC, transcription factors (NF-kappaB, STAT3, and insulin. In validation studies, western blot analysis in splenic B cells from 5-month-old NZB/NZW F1 lupus mice showed activation of STAT3, ITGB2, HSPB1, ERK, JNK, p38, and p32 kinases, and downregulation of FOXO3 and VDR compared to normal C57Bl/6 mice. CONCLUSIONS/SIGNIFICANCE: Gene network analysis of lupus BMMCs identified central gene regulators implicated in disease pathogenesis which could represent targets of novel therapies in human SLE. The high similarity between active SLE and NHL networks provides a molecular basis for the reported association of the former with lymphoid malignancies.

  20. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

  1. Residual γH2AX foci as an indication of lethal DNA lesions

    Directory of Open Access Journals (Sweden)

    Banuelos C Adriana

    2010-01-01

    Full Text Available Abstract Background Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. Methods To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. Results For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Conclusion Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.

  2. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  3. Localized air foci in the lower thorax in the patients with pneumothorax: Skip pneumothoraces

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Takeshi, E-mail: higuchi@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Takahashi, Naoya, E-mail: nandtr@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Kiguchi, Takao, E-mail: takakig@gmail.com [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan); Shiotani, Motoi, E-mail: Shiotani14@gmail.com [Department of Radiology, Niigata Cancer Center Hospital, 2-15-3 Chuo-ku, Kawagishicho, Niigata 951-8566 (Japan); Maeda, Haruo, E-mail: h-maeda@hosp.niigata.niigata.jp [Department of Diagnostic Radiology, Niigata City General Hospital, 463-7 Chuo-ku, Shumoku, Niigata 950-1197 (Japan)

    2013-08-15

    Purpose: To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Materials and methods: Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1–93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ{sup 2} test. All P values <0.05 were considered significant. Results: Localized air foci in the lower thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Conclusion: Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases.

  4. Use of Single- versus Multiple-Fraction Palliative Radiation Therapy for Bone Metastases: Population-Based Analysis of 16,898 Courses in a Canadian Province

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Robert A., E-mail: rolson2@bccancer.bc.ca [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Tiwana, Manpreet S. [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); Barnes, Mark [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); Kiraly, Andrew; Beecham, Kwamena [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); Miller, Stacy [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Hoegler, David [University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency Centre for the Southern Interior, Kelowna, British Columbia (Canada); Olivotto, Ivo [University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency Vancouver Centre, Victoria, British Columbia (Canada)

    2014-08-01

    Purpose: There is abundant evidence that a single fraction (SF) of palliative radiation therapy (RT) for bone metastases is equivalent to more protracted and costly multiple fraction courses. Despite this, there is low utilization of SFRT internationally. We sought to determine the utilization of SFRT in a population-based, publicly funded health care system. Methods and Materials: All consecutive patients with bone metastases treated with RT during 2007 to 2011 in British Columbia (BC) were identified. Associations between utilization of SFRT and patient and provider characteristics were investigated. Results: A total of 16,898 courses of RT were delivered to 8601 patients. SFRT was prescribed 49% of the time. There were positive relationships among SFRT utilization and primary tumor group (P<.001; most commonly in prostate cancer), worse prognosis (P<.001), increasing physician experience (P<.001), site of metastases (P<.001; least for spine metastases), and area of training (P<.001; most commonly for oncologists trained in the United Kingdom). There was wide variation in the prescription of SFRT across 5 regional cancer centers, ranging from 25.5% to 73.4%, which persisted after controlling for other, potentially confounding factors (P<.001). Conclusions: The large variability in SFRT utilization across BC Cancer Agency (BCCA) cancer centers suggests there is a strong cultural effect, where physicians' use of SFRT is influenced by their colleagues' practice. SFRT use in BC was similar to that in other Canadian and western European reports but strikingly higher than in the United States. Further work is needed to standardize SFRT prescribing practices internationally for this common indication for RT, with the potential for huge health system cost savings and substantial improvements in patients' quality of life.

  5. GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment.

    Science.gov (United States)

    Podar, Klaus; Catley, Laurence P; Tai, Yu-Tzu; Shringarpure, Reshma; Carvalho, Pedro; Hayashi, Toshiaki; Burger, Renate; Schlossman, Robert L; Richardson, Paul G; Pandite, Lini N; Kumar, Rakesh; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C

    2004-05-01

    Previous studies have shown that the multiple myeloma (MM) cell line and MM patient cells express high-affinity vascular endothelial growth factor (VEGF) receptor-1 or Fms-like tyrosine kinase-1 (Flt-1) but not VEGF receptor-2 or Flk-1/kinase insert domain-containing receptor (Flk-1/KDR) and that VEGF triggers MM cell proliferation through a mitogen-activated protein kinase (MAPK)-dependent pathway and migration through a protein kinase C (PKC)-dependent pathway. The present study evaluates the efficacy of the small molecule tyrosine-kinase inhibitor GW654652, which inhibits all 3 VEGF receptors with similar potency. We show that GW654652 acts directly on MM cells and in the bone marrow microenvironment. Specifically, GW654652 (1-10 microg/mL) inhibits, in a dose-dependent fashion, VEGF-triggered migrational activity and cell proliferation of MM cell lines that are sensitive and resistant to conventional therapy. As expected from our previous studies of VEGF-induced signaling and sequelae in MM cells, GW654652 blocked VEGF-induced Flt-1 phosphorylation and downstream activation of AKT-1 and MAPK-signaling cascades. Importantly, GW654652 also inhibits interleukin-6 and VEGF secretion and proliferation of MM cells induced by tumor cell binding to bone marrow (BM) stromal cells. The activity of a pan-VEGF receptor inhibitor against MM cells in the BM milieu, coupled with its lack of major toxicity in preclinical mouse models, provides the framework for clinical trials of this drug class to improve patient outcome in MM.

  6. Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

    Directory of Open Access Journals (Sweden)

    Meißner Tobias

    2010-05-01

    Full Text Available Abstract Background Multiple myeloma (MM is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC. In the past few years, many myeloma growth factors (MGF have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them. Methods We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts. Results 4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC and BM plasma cell (BMPC compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC. Conclusions Two major messages arise from this analysis 1 The majority of MGF genes is expressed by the bone marrow environment. 2 Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.

  7. Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis.

    Science.gov (United States)

    Femia, Angelo Pietro; Dolara, Piero; Caderni, Giovanna

    2004-02-01

    Crypt foci with absent or scant mucous production (mucin-depleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg x 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number of MDF was significantly increased in rats treated with CHA (PMDF/colon were 6.10 +/- 1.26, 10.59 +/- 1.96 and 1.31 +/- 0.21 in controls, CHA and PXC groups, respectively, means +/- SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of 'large' MDF, formed by 12 or more crypts, was also reduced (PMDF were 1.7 +/- 0.5 and 0.4 +/- 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.

  8. [Bone transplant].

    Science.gov (United States)

    San Julián, M; Valentí, A

    2006-01-01

    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands.

  9. Incidence and imaging characteristics of skeletal metastases detected by bone scintigraphy in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Jauković Ljiljana

    2006-01-01

    Full Text Available Background/Aim. Detection of metastatic bone disease by skeletal scintigraphy is a classical application of nuclear medicine in cancer patients. Detection of bone metastases in patients with lung cancer is necessary for an appropriate treatment modality. The aim of this study was to report the frequency and imaging characteristics of bone metastases detected by bone scintigraphy (BS using technetium-99m phosphonates in patients with lung cancer. Methods. We retrospectively analyzed a total of one hundred patients (78 males and 22 females, mean age of 63.3 years, with the diagnosis of lung cancer, who underwent BS during a three-year period (2003−2005. Scintiscans were classified as positive, negative and suspicious with regard to the presence of bone metastases. Results. The incidence of positive, negative and suspicious findings were 57%. 32% and 11%, respectively. Out of 57 patients with bone metastases, 51 had multiple asymmetric foci of increased tracer activity localized in the ribs, spine, extremities, pelvis, sternum, scapula and skull in 72%, 54%, 49%, 37%, 12%, 9% and 5% of scans, respectively. BS revealed solitary metastases in 6 of the patients. The lesions were located in the lower limbs in three patients and in the upper limbs, pelvis and sternum in the remaining three patients. Conclusion. Bone scintigraphy plays a significant role in staging and selecting of patients for curative lung surgery. Due to the fact that metastatic involvment of the extremities was frequently shown, our study suggests that systematic inclusion of the limbs in BS acquisition should be obligatory.

  10. Localized air foci in the lower thorax in the patients with pneumothorax: skip pneumothoraces.

    Science.gov (United States)

    Higuchi, Takeshi; Takahashi, Naoya; Kiguchi, Takao; Shiotani, Motoi; Maeda, Haruo

    2013-08-01

    To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1-93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ(2) test. All P values thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development.

    Directory of Open Access Journals (Sweden)

    Lise Michel

    Full Text Available Myotonic dystrophy type 1 (DM1 is caused by an unstable expanded CTG repeat located within the DMPK gene 3'UTR. The nature, severity and age at onset of DM1 symptoms are very variable in patients. Different forms of the disease are described, among which the congenital form (CDM is the most severe. Molecular mechanisms of DM1 are well characterized for the adult form and involve accumulation of mutant DMPK RNA forming foci in the nucleus. These RNA foci sequester proteins from the MBNL family and deregulate CELF proteins. These proteins are involved in many cellular mechanisms such as alternative splicing, transcriptional, translational and post-translational regulation miRNA regulation as well as mRNA polyadenylation and localization. All these mechanisms can be impaired in DM1 because of the deregulation of CELF and MBNL functions. The mechanisms involved in CDM are not clearly described. In order to get insight into the mechanisms underlying CDM, we investigated if expanded RNA nuclear foci, one of the molecular hallmarks of DM1, could be detected in human DM1 fetal tissues, as well as in embryonic and neonatal tissues from transgenic mice carrying the human DMPK gene with an expanded CTG repeat. We observed very abundant RNA foci formed by sense DMPK RNA and, to a lesser extent, antisense DMPK RNA foci. Sense DMPK RNA foci clearly co-localized with MBNL1 and MBNL2 proteins. In addition, we studied DMPK sense and antisense expression during development in the transgenic mice. We found that DMPK sense and antisense transcripts are expressed from embryonic and fetal stages in heart, muscle and brain and are regulated during development. These results suggest that mechanisms underlying DM1 and CDM involved common players including toxic expanded RNA forming numerous nuclear foci at early stages during development.

  12. Bone marrow mast cell density correlates with serum levels of VEGF and CXC chemokines ENA-78 and GRO-α in multiple myeloma.

    Science.gov (United States)

    Pappa, C A; Tsirakis, G; Devetzoglou, M; Zafeiri, M; Vyzoukaki, R; Androvitsanea, A; Xekalou, A; Sfiridaki, K; Alexandrakis, M G

    2014-06-01

    Angiogenesis is a crucial process in growth and progression of multiple myeloma (MM). Mast cells (MCs) play an important role in MM angiogenesis. Various angiogenic mediators secreted by MCs regulate endothelial cell proliferation and function. Among them, ELR(+) CXC chemokines, such as growth-related oncogen-alpha (GRO-α) and epithelial neutrophil activating protein-78 (ENA-78), have been described as potential mediators in regulation of angiogenesis. The purpose of the study was to quantify MCs in bone marrow (BM) biopsies of MM patients, expressed as MC density (MCD), and correlate it with serum concentrations of vascular endothelial factor (VEGF), GRO-α, ENA-78. Fifty-four newly diagnosed MM patients and 22 healthy controls were studied. Tryptase was used for the immunohistochemical stain of MCs. VEGF, GRO-α, and ENA-78 were measured in sera by ELISA. MCD and serum levels of GRO-α, ENA-78, and VEGF were significantly higher in MM patients compared to controls (pENA-78. These findings support that MCs participate in the pathophysiology of MM and is implicated in the angiogenic process and disease progression.

  13. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  14. Spatial distribution of schistosomiasis foci on Itamaracá Island, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    CS Barbosa

    2004-08-01

    Full Text Available Acute cases of schistosomiasis have been found on the coastal area of Pernambuco, Brazil, due to environmental disturbances and disorderly occupation of the urban areas. This study identifies and spatially marks the main foci of the snail host species, Biomphalaria glabrata on Itamaracá Island. The chaotic occupation of the beach resorts has favoured the emergence of transmission foci, thus exposing residents and tourists to the risk of infection. A database covering five years of epidemiological investigation on snails infected by Schistosoma mansoni in the island was produced with information from the geographic positioning of the foci, number of snails collected, number of snails tested positive, and their infection rate. The spatial position of the foci were recorded through the Global Positioning System (GPS, and the geographical coordinates were imported by AutoCad. The software packages ArcView and Spring were used for data processing and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and areas of environmental risk were identified and spatially analyzed allowing the identification of the areas exposed to varying degrees of risk.

  15. A rat liver foci promotion study with 50-Hz magnetic fields.

    Science.gov (United States)

    Rannug, A; Holmberg, B; Mild, K H

    1993-08-01

    To investigate the possible tumor-promoting effect of magnetic fields (MF), we have performed two liver foci bioassays in rats which were exposed to MF at four flux density levels (0.5 microT, 5 microT, 0.05 mT, and 0.5 mT). The MF were generated in exposure equipment consisting of copper coils surrounding racks with animal cages and giving homogenous horizontal 50-Hz magnetic fields. Rats previously submitted to partial hepatectomy and diethylnitrosamine treatment were exposed to MF for 12 weeks. Exposed and control rats were kept in separate rooms. As a positive control phenobarbital (PB) was administered for 12 weeks. The number, area, and volume of foci expressing gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST-p) were evaluated. The body weight gains and relative liver weights of MF-exposed rats were not different as compared to control rats. There was a slight increase in GGT-staining foci, but not in GST-p-staining foci, in the groups exposed to flux densities of 0.5 microT and 0.05 mT compared to the control group in the first experiment. The number of both GGT- and GST-p-staining foci in the livers of all MF-exposed groups were, however, within the control range when the results of the two experiments were considered together.

  16. Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Zhenyu Fan; Yongqin Zhang; Yuxia Yang; Yaqing Liu; Xiaoli Dang; Wenjun Song; Yinping Wu; Jiang Ye

    2013-01-01

    One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal foci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy. Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

  17. Formation of Subnuclear Foci Is a Unique Spatial Behavior of Mating MAPKs during Hyperosmotic Stress

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2013-02-01

    Full Text Available The assembly of signaling components and transcription factors in ordered subcellular structures is increasingly implicated as an important regulatory strategy for modulating the activity of cellular pathways. Here, we document the inducible formation of subnuclear foci formed by two mitogen-activated protein kinases (MAPKs in Saccharomyces cerevisiae upon hyperosmotic stress. Specifically, we demonstrate that activation of the hyperosmotic stress response pathway induces the mating pathway MAPK Fus3 and the filamentation pathway MAPK Kss1 to form foci in the nucleus that are organized by their shared downstream transcription factor Ste12. Foci formation of colocalized Ste12, Fus3, and Kss1 requires the kinase activity of the hyperosmotic response MAPK Hog1 and correlates with attenuated signaling in the mating pathway. Conversely, activation of the mating pathway prevents foci formation upon subsequent hyperosmotic stress. These results suggest that Hog1-mediated spatial localization of Fus3 and Ste12 into subnuclear foci could contribute to uncoupling the pheromone and osmolarity pathways, which share signaling components, under high-osmolarity conditions.

  18. New acquisitions in the physiopathology of multiple myeloma: role of the bone microenvironment Novos conhecimentos da fisiopatologia do mieloma múltiplo: o papel do microambiente medular

    Directory of Open Access Journals (Sweden)

    Nicola Giuliani

    2008-06-01

    Full Text Available Multiple myeloma (MM is a plasma cell malignancy characterized by the accumulation of malignant plasma cells within the bone marrow (BM. MM cells interact with the microenvironment and induce pathological modifications that in turn support the growth and survival of MM cells. The BM microenvironment consists of various extracellular matrix proteins, and cell components as haematopoietic stem cells, progenitor and precursor cells, immune cells, erythrocytes, BM stromal cells (BMSCs, BM endothelial cells, as well as osteoclasts and osteoblasts that are able to secret several growth factors for MM cells. The direct interactions of MM cells with the microenvironment and the secreted cytokines activate signalling pathways mediating growth, survival, drug resistance and the migration of MM cells as well as osteoclastogenesis and angiogenesis. In this article we underline in particular the new evidences at the basis of the interaction between MM cell and bone cells and the potential role of osteoclast and osteoblast in MM pathophysiology.O mieloma múltiplo (MM é uma doença maligna das células plasmáticas caracterizada pelo acúmulo de células plasmáticas na medula óssea (MO. As células do MM interagem com o microambiente e induzem modificações patológicas que, por seu turno, propiciam o crescimento e a sobrevida das células do MM. O microambiente da MO consiste de várias proteínas da matriz extracelular e de componentes hematopoéticos: células-tronco, progenitoras e precursoras, células imunes, eritrocitárias, estromais, endoteliais. Possuem também osteoclastos e osteoblastos capazes de secreção de fatores de crescimento das células do MM. A direta interação das células mielomatosas com o microambiente e a secreção de citocinas ativam cascatas sinalizadoras que mediam o crescimento, sobrevida, resistência a drogas e a migração destas células assim como a osteoclastogênese e a angiogênese. Neste artigo explicitamos

  19. Identification of Senescent Cells in the Bone Microenvironment

    Science.gov (United States)

    Farr, Joshua N; Fraser, Daniel G; Wang, Haitao; Jaehn, Katharina; Ogrodnik, Mikolaj B; Weivoda, Megan M; Drake, Matthew T; Tchkonia, Tamara; LeBrasseur, Nathan K; Kirkland, James L; Bonewald, Lynda F; Pignolo, Robert J; Monroe, David G; Khosla, Sundeep

    2017-01-01

    Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16Ink4a, profound secretome changes, telomere shortening, and decondensation of pericentromeric satellite DNA. Because senescent cells accumulate in multiple tissues with aging, these cells and the dysfunctional factors they secrete, termed the senescence-associated secretory phenotype (SASP), are increasingly recognized as promising therapeutic targets to prevent age-related degenerative pathologies, including osteoporosis. However, the cell type(s) within the bone microenvironment that undergoes senescence with aging in vivo has remained poorly understood, largely because previous studies have focused on senescence in cultured cells. Thus in young (age 6 months) and old (age 24 months) mice, we measured senescence and SASP markers in vivo in highly enriched cell populations, all rapidly isolated from bone/marrow without in vitro culture. In both females and males, p16Ink4a expression by real-time quantitative polymerase chain reaction (rt-qPCR) was significantly higher with aging in B cells, T cells, myeloid cells, osteoblast progenitors, osteoblasts, and osteocytes. Further, in vivo quantification of senescence-associated distension of satellites (SADS), ie, large-scale unraveling of pericentromeric satellite DNA, revealed significantly more senescent osteocytes in old compared with young bone cortices (11% versus 2%, p < 0.001). In addition, primary osteocytes from old mice had sixfold more (p < 0.001) telomere dysfunction-induced foci (TIFs) than osteocytes from young mice. Corresponding with the age-associated accumulation of senescent osteocytes was significantly higher expression of multiple SASP markers in osteocytes from old versus young mice, several of which also showed dramatic age-associated upregulation in myeloid cells. These data show that with aging, a subset of cells

  20. A Review of Impact of Bam Earthquake on Cutaneous Leishmaniasis and Status: Epidemic of Old Foci, Emergence of New Foci and Changes in Features of the Disease

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Aflatoonian

    2016-01-01

    Full Text Available Background: Global findings indicate that incidence rate of cutaneous leishmaniasis (CL has significantly in­creased during the past decade, as documented in many countries. This review was aimed to evaluate the trend of CL cases in terms of demographic and clinical characteristics during a decade after the earthquake (2003–2012 com­pared to the corresponding period before the earthquake in Bam (1993–2003.Methods: Direct smear preparations along with different intrinsic methods were used for detection and identification of the causative agents.Results: Overall, 20999 cases of CL have occurred during the last 20 years (1993–2012, 6731 cases before and 14268 cases after the earthquake (P< 0.001.Conclusions: Following a major earthquake, several risk factors could activate epidemics of cutaneous leishmaniasis in old foci and induce emerging foci in new areas.

  1. Desmoplastic fibroma of bone: MRI features

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, F.M. [Department of Radiology, University Hospital Antwerp, Edegem (Belgium); Department of Radiology, AZ Sint Maarten, Duffel (Belgium); Hauben, E.; Van Marck, E. [Department of Pathology, University Hospital Antwerp, Edegem (Belgium); De Beuckeleer, L.H.; De Schepper, A.M. [Department of Radiology, University Hospital Antwerp, Edegem (Belgium); Willemen, D. [Department of Orthopaedic Surgery, AZ Sint Maarten, Duffel (Belgium)

    2000-03-30

    Desmoplastic fibroma of bone is a very rare benign tumor, which may be locally aggressive. In contrast to the well-documented radiological appearance, the literature on MR imaging features of this tumor is scarce. The MR imaging characteristics in our case are compared to those previously reported. Although there is a considerable overlap in the MR imaging features with other bone tumors, an interesting MR feature of desmoplastic fibroma is the presence of low to intermediate signal intensity foci on T2-weighted images, which radiographically does not correspond to calcifications. This feature may help narrow the differential diagnosis. (orig.)

  2. [THE PRESENT STATE OF EPIZOOTOLOGICAL MONITORING OF THE NATURAL FOCI OF INFECTIONS IN THE RUSSIAN FEDERATION].

    Science.gov (United States)

    Trankvilevsky, D V; Tsarenko, V A; Zhukov, V I

    2016-01-01

    The facilities of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare play a leading role in epizootological monitoring. The specialists (zoologists and entomologists) of Hygiene and Epidemiology Centers do basic work in the subjects of the Russian Federation. The data obtained in the participation of different ministries and departments are used to analyze the results of monitoring. The latter is one of the important steps in the management of the epidemic, process in natural focal infections. In recent years, there has been an unjustified reduction in the volume of studies in the natural foci. This negatively affects the reliability of estimates and predictions of the epidemic activity of the natural foci of infections. Ensuring the national, security of the Russian Federation, epidemiological surveillance, and control of its natural foci requires staffing and appropriate professional training in the zoological and entomological subdivisions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare.

  3. Identification of Chinese plague foci from long-term epidemiological data.

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C

    2012-05-22

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed.

  4. Identification of Chinese plague foci from long-term epidemiological data

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C.

    2012-01-01

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed. PMID:22570501

  5. Dosing related effects of zoledronic acid on bone markers and creatinine clearance in patients with multiple myeloma and metastatic breast cancer

    DEFF Research Database (Denmark)

    Søe, Kent; Delaissé, Jean-Marie; Jakobsen, Erik H;

    2014-01-01

    phase II clinical trial we investigated the effect of Zol treatment on the serum levels of the bone markers collagen type 1 cross-linked C-telopeptide (CTX) and bone specific alkaline phosphatase (bALP) as well as on creatinine clearance (kidney function) in response to dosing and duration of treatment...

  6. A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma

    DEFF Research Database (Denmark)

    Søndergaard, Teis Esben; Pedersen, PT; Levin Andersen, Thomas;

    2008-01-01

    Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease a...

  7. SPO11-independent DNA repair foci and their role in meiotic silencing.

    Directory of Open Access Journals (Sweden)

    Fabrizia Carofiglio

    2013-06-01

    Full Text Available In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI. A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC, is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11(YF/YF, and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11(YF/YF and Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number of repair foci increased during oocyte development, indicating the induction of S phase-independent, de novo DNA damage. In wild type pachytene oocytes we observed meiotic silencing in two types of pseudo XY bodies, one type containing DMC1 and RAD51 foci on unsynapsed axes, and another type containing only RAD51 foci, mainly on synapsed axes. Taken together, our results indicate that in addition to asynapsis, persistent SPO11-induced DSBs are important for the initiation of MSCI and MSUC, and that SPO11-independent DNA repair foci contribute to the MSUC response in oocytes.

  8. SPO11-independent DNA repair foci and their role in meiotic silencing.

    Science.gov (United States)

    Carofiglio, Fabrizia; Inagaki, Akiko; de Vries, Sandra; Wassenaar, Evelyne; Schoenmakers, Sam; Vermeulen, Christie; van Cappellen, Wiggert A; Sleddens-Linkels, Esther; Grootegoed, J Anton; Te Riele, Hein P J; de Massy, Bernard; Baarends, Willy M

    2013-06-01

    In mammalian meiotic prophase, the initial steps in repair of SPO11-induced DNA double-strand breaks (DSBs) are required to obtain stable homologous chromosome pairing and synapsis. The X and Y chromosomes pair and synapse only in the short pseudo-autosomal regions. The rest of the chromatin of the sex chromosomes remain unsynapsed, contains persistent meiotic DSBs, and the whole so-called XY body undergoes meiotic sex chromosome inactivation (MSCI). A more general mechanism, named meiotic silencing of unsynapsed chromatin (MSUC), is activated when autosomes fail to synapse. In the absence of SPO11, many chromosomal regions remain unsynapsed, but MSUC takes place only on part of the unsynapsed chromatin. We asked if spontaneous DSBs occur in meiocytes that lack a functional SPO11 protein, and if these might be involved in targeting the MSUC response to part of the unsynapsed chromatin. We generated mice carrying a point mutation that disrupts the predicted catalytic site of SPO11 (Spo11(YF/YF)), and blocks its DSB-inducing activity. Interestingly, we observed foci of proteins involved in the processing of DNA damage, such as RAD51, DMC1, and RPA, both in Spo11(YF/YF) and Spo11 knockout meiocytes. These foci preferentially localized to the areas that undergo MSUC and form the so-called pseudo XY body. In SPO11-deficient oocytes, the number of repair foci increased during oocyte development, indicating the induction of S phase-independent, de novo DNA damage. In wild type pachytene oocytes we observed meiotic silencing in two types of pseudo XY bodies, one type containing DMC1 and RAD51 foci on unsynapsed axes, and another type containing only RAD51 foci, mainly on synapsed axes. Taken together, our results indicate that in addition to asynapsis, persistent SPO11-induced DSBs are important for the initiation of MSCI and MSUC, and that SPO11-independent DNA repair foci contribute to the MSUC response in oocytes.

  9. High-resolution CT features of bleeding foci in patients with massive hemoptysis

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Keum Soo; Lee, Ki Nam; Jung, Won Jung; Kim, Jae Ic; Kang, Myong Jin; Park, Byeong Ho [Donga Univ. College of Medicine, Pusan (Korea, Republic of)

    2000-12-01

    To compare the high-resolution CT features of bleeding foci in patients with massive hemoptysis during embolization with those revealed by angiography. Between June 1997 and June 1999, we evaluated 25 patients who from among a total of 49 with arterial embolization due to massive hemoptysis underwent HRCT prior to embolization. We retrospectively analyzed medical records, and angiographic and HRCT findings. The time interval between HRCT and arterial embolization varied from two hours to six days. Angiography indicated that the bronchial, intercostal and internal mammary artery, and branches of the subclavian, were the foci of bleeding, and indicated the location of these in each pulmonary lobe. The HRCT findings were evaluated in terms of cavity, air-meniscus sign, bronchial dilatation, consolidation, ground-glass opacity, and fibrotic scar. We anlayzed the corresponding sites of HRCT and the angiographic findings of the foci of bleeding. In 24 of 25 patients, the foci of bleeding were angiographically confirmed, their presence being noted in 28 pulmonary lobes. HRCT findings corresponding to the bleeding foci revealed by angiography were the air-meniscus sign (8 of 10 lobes, 80.0%), cavity (7 of 9 lobes, 77.8%), bronchial dilatation (21 of 30 lobes, 70.0%), and fibrotic scar (1 of 23 lobes, 4.3%). The findings in areas of consolidation and/or ground-glass opacity only did not correspond, however. As compared with those revealed by angiography, the HRCT features of bleeding foci in patients with massive hemoptysis during embolization are in order of frequency, the air-meniscus sign, cavity, and bronchial dilatation.

  10. Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.

    Science.gov (United States)

    Takamatsu, Hiroyuki; Ogawa, Yoshiyasu; Kobayashi, Noriko; Obata, Kazue; Narisawa, Tadashi; Nakayama, Kouji; Munemoto, Saori; Aoki, Go; Ohata, Kinya; Kumano, Yoshihisa; Ozaki, Jun; Murata, Ryoichi; Kondo, Yukio; Terasaki, Yasushi; Kurokawa, Toshiro; Miyamoto, Toshihiro; Shimizu, Naomi; Fukushima, Toshihiro; Yoshida, Akira; Ueda, Takanori; Yoshida, Takashi; Nakao, Shinji

    2013-10-01

    Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

  11. Elevated expression of APE1/Ref-1 and its regulation on IL-6 and IL-8 in bone marrow stromal cells of multiple myeloma.

    Science.gov (United States)

    Xie, Jia-Yin; Li, Meng-Xia; Xiang, De-Bing; Mou, Jiang-Hong; Qing, Yi; Zeng, Lin-Li; Yang, Zhen-Zhou; Guan, Wei; Wang, Dong

    2010-10-01

    A number of growth factors secreted by bone marrow stromal cells (BMSCs), including interleukin-6 and -8 (IL-6/8), are important for the initiation and progression of multiple myeloma (MM). However, the mechanisms that regulate the production of IL-6/8 by BMSC have not yet been well characterized. Human dual functional protein apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is essential for cell survival and proliferation. Previous studies showed that APE1/Ref-1 was overexpressed in tumor cells, but few studies showed its expression in supportive cells in the tumor microenvironment. We first detected APE1/Ref-1 expression in BMSCs of normal, initial, and recurrent MM patients, and then explore the correlation between APE1/Ref-1 level and IL-6/8 secretion of BMSCs. A marked increase of APE1/Ref-1 expression and abnormal subcellular distribution were observed in MM BMSCs. APE1/Ref-1 overexpression was related to higher secretary level of IL-6/8 by MM BMSCs and the IL-6/8 secretion was blocked significantly by adenovirus-mediated APE1/Ref-1-specific (small interfering RNA) siRNA. Our results also demonstrated that APE1/Ref-1-specific siRNA significantly inhibited DNA binding activity of AP-1 and nuclear factor-κB (NF-κB), 2 important transcription factors in the regulation IL-6/8 secretion in MM BMSCs. The results provided by the present study indicate APE1/Ref-1, which plays a regulatory role in IL-6/8 production by BMSCs, may be a potential therapeutic target of MM.

  12. Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle.

    Science.gov (United States)

    Makar, Tapas K; Bever, Christopher T; Singh, Ishwar S; Royal, Walter; Sahu, Surasri Nandan; Sura, Tushar P; Sultana, Shireen; Sura, Karna T; Patel, Niraj; Dhib-Jalbut, Suhayl; Trisler, David

    2009-05-29

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is neuroprotective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the central nervous system (CNS), when delivered peripherally, is limited due to the blood-brain barrier (BBB). We have developed a means of delivering BDNF into the CNS using genetically engineered bone marrow stem cells (BMSCs) as a vehicle, and have explored the clinical effects of BDNF on outcomes in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). BDNF-engineered-BMSCs were transplanted (i.v.) into irradiated 2-week-old SJL/J female mice. Eight weeks after transplantation, mice were immunized with a peptide of proteolipid protein (PLP(139-151)). Mice, which had received BDNFengineered BMSCs, showed a significant delay in EAE onset and a reduction in overall clinical severity compared to mice receiving BMSC transfected with an empty vector lacking the BDNF gene. In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination. Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group. These results support the use of BMSCs as vehicles to deliver BDNF into the CNS of EAE animals. This is a potentially novel therapeutic approach that might be used to deliver BDNF gene or genes for other therapeutic proteins into the CNS in MS or in other diseases of the CNS in which accessibility of therapeutic proteins is limited due to the BBB.

  13. Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature.

    Science.gov (United States)

    Zhang, Wei-dong; Liu, Da-ren; Feng, Cheng-cheng; Zhou, Chuan-biao; Zhan, Chen-ni; Que, Ri-sheng; Chen, Li

    2014-12-01

    Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42-72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I(131) adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.

  14. Genetics Home Reference: multiple myeloma

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions multiple myeloma multiple myeloma Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Multiple myeloma is a cancer that develops in the bone ...

  15. 人工骨材料修复骨缺损:多种复合后的生物学与力学特征%Artificial bone materials for bone defect repair:biomechanical characteristics of multiple composites

    Institute of Scientific and Technical Information of China (English)

    杨毅; 毕鑫; 李多玉; 唐一萍; 李彪

    2014-01-01

    背景:当前应用广泛的骨缺损修复方式主要有自体骨移植、异体骨移植和人工骨移植,人工骨移植可避免患者自身取材的痛苦和并发症及同种异体骨免疫排斥的危险。目的:综述近几年来国内外常用的几种人工骨材料的研究进展情况。方法:应用计算机检索2007至2013年中国期刊全文数据库、PubMed 数据库、中国生物医学文献数据库、FMJS 数据库中有关人工骨材料的研究。中文检索词为“人工骨,材料,骨缺损,骨移植”,英文检索词为“artificial bone,material,bone defect,bone graft”。结果与结论:目前常用的人工骨材料有天然高分子材料、人工合成高分子、无机材料、纳米材料。理想的骨移植替代物应该具备以下条件:良好的生物相容性;局部形成微酸性生物环境;利于血管和成骨细胞长入;可完全生物降解;兼具骨生成性、骨传导性和骨诱导性。生物蛋白胶降解及组织相容性较好,且可塑形,但强度较差,以后研究方向主要为加强其强度。人工合成及无机材料强度及支架作用较好,但组织相容性较差,提高其组织相容性很重要。纳米材料为较合适的人工骨材料。目前应用于骨组织工程研究的人工骨材料均有各自的长处和不足,尚不能同时满足理想的骨组织工程细胞外基质材料各方面的要求,而且在生物学和力学特性上与天然骨有差异,故将多种类型材料复合并进行结构和功能修饰,是研制理想骨缺损修复材料的方向。%BACKGROUND:The current widely used methods of bone defect repair mainly include bone autograft, alograft and artificial bone transplantation. Artificial bone graft can avoid the pain resulting from taking patients’ own materials, complications and risk of alograft immune rejection. OBJECTIVE:To review the research progress in some commonly used artificial bone

  16. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J. M.; Span, L. F. R.; Stokman, M. A.; van Winkelhoff, A. J.; Vissink, A.; Spijkervet, F. K. L.

    2016-01-01

    Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect o

  17. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    NARCIS (Netherlands)

    Schuurhuis, J M; Span, L. F. R.; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

    2016-01-01

    BACKGROUND: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect o

  18. Repair of abnormal perfusion foci in idiopathic epilepsy patients under long-term antiepileptic treatment

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Siyu Zhao; Yaqing Liu

    2011-01-01

    Epileptic seizure control and the disappearance of epileptiform discharge are not indicative of the absence of abnormal perfusion foci.Perfusion abnormalities are a major cause of epileptic discharge, and the existence of abnormal perfusion foci implies possible relapse.Very little is known about perfusion abnormality repair in epilepsy.The present study selected 43 cases of idiopathic epilepsy under antiepileptic drug control for an average of 24 months.Comparisons between interictal single-photon emission CT (SPECT)images and long-term electroencephalogram (EEG) pre- and post-treatment showed that cases of normal SPECT increased by 48% (12/25) following treatment, with a total number of 15 reduced foci (36%, 15/41).Perfusion foci, i.e., region of interest, were altered following treatment.These changes included:normal to abnormal in 3 cases (7%, 3/43; 2 hyperperfusion and 1 hypoperfusion); abnormal to normal in 14 cases (32%, 14/43; 10 pre-treatment hypoperfusion and 4 hyperperfusion); abnormal to abnormal in 7 cases (16%, 7/43; hyperperfusion to hypoperfusion in 5 cases, hypoperfusion to hyperperfusion in 2 cases).Long-term EEG revealed in an increase in the number of normal cases by 20 (40%, 20/39), and there were 25 fewer cases with epileptiform discharges (66%, 25/38).These findings demonstrate that long-term control of anti-epileptic drugs partially repaired cerebral perfusion abnormalities and reduced epileptiform discharges in idiopathic epilepsy.

  19. Sandfly fauna of endemic leishmaniasis foci in Anzoátegui State, Venezuela.

    Science.gov (United States)

    González, R; Jorquera, A; De Sousa, L; Ledezma, E; Devera, R

    2002-01-01

    A census of the sandfly fauna was undertaken in 1993-98 in 5 endemic leishmaniasis foci situated at different altitudes in Anzoátegui State, Venezuela. From the 17 species of Lutzomyia identified, we believe that Lu. ovallesi, Lu. panamensis and Lu. gomezi are the probable vectors of cutaneous leishmaniasis, while Lu. evansi might transmit visceral leishmaniasis.

  20. Genetic micro-heterogeneity of Leishmania major in emerging foci of zoonotic cutaneous leishmaniasis in Tunisia.

    Science.gov (United States)

    Attia, Hanene; Sghaier, Rabiaa M; Gelanew, Tesfaye; Bali, Aymen; Schweynoch, Carola; Guerfali, Fatma Z; Mkannez, Ghada; Chlif, Sadok; Belhaj-Hamida, Nabil; Dellagi, Koussay; Schönian, Gabriele; Laouini, Dhafer

    2016-09-01

    Tunisia is endemic for zoonotic cutaneous leishmaniasis (ZCL), a parasitic disease caused by Leishmania (L.) major. ZCL displays a wide clinical polymorphism, with severe forms present more frequently in emerging foci where naive populations are dominant. In this study, we applied the multi-locus microsatellite typing (MLMT) using ten highly informative and discriminative markers to investigate the genetic structure of 35 Tunisian Leishmania (L.) major isolates collected from patients living in five different foci of Central Tunisia (two old and three emerging foci). Phylogenetic reconstructions based on genetic distances showed that nine of the ten tested loci were homogeneous in all isolates with homozygous alleles, whereas one locus (71AT) had a 58/64-bp bi-allelic profile with an allele linked to emerging foci. Promastigote-stage parasites with the 58-bp allele tend to be more resistant to in vitro complement lysis. These results, which stress the geographical dependence of the genetic micro-heterogeneity, may improve our understanding of the ZCL epidemiology and clinical outcome.

  1. S phase progression in human cells is dictated by the genetic continuity of DNA foci.

    Directory of Open Access Journals (Sweden)

    Apolinar Maya-Mendoza

    2010-04-01

    Full Text Available DNA synthesis must be performed with extreme precision to maintain genomic integrity. In mammalian cells, different genomic regions are replicated at defined times, perhaps to preserve epigenetic information and cell differentiation status. However, the molecular principles that define this S phase program are unknown. By analyzing replication foci within discrete chromosome territories during interphase, we show that foci which are active during consecutive intervals of S phase are maintained as spatially adjacent neighbors throughout the cell cycle. Using extended DNA fibers, we demonstrate that this spatial continuity of replication foci correlates with the genetic continuity of adjacent replicon clusters along chromosomes. Finally, we used bioinformatic tools to compare the structure of DNA foci with DNA domains that are seen to replicate during discrete time intervals of S phase using genome-wide strategies. Data presented show that a major mechanism of S phase progression involves the sequential synthesis of regions of the genome because of their genetic continuity along the chromosomal fiber.

  2. Bone scan

    Science.gov (United States)

    ... legs, or spine fractures) Diagnose a bone infection (osteomyelitis) Diagnose or determine the cause of bone pain, ... 2015:chap 43. Read More Broken bone Metabolism Osteomyelitis Review Date 12/10/2015 Updated by: Jatin ...

  3. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  4. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  5. Bone Markers

    Science.gov (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  6. IKAROS expression in distinct bone marrow cell populations as a candidate biomarker for outcome with lenalidomide-dexamethasone therapy in multiple myeloma.

    Science.gov (United States)

    Bolomsky, Arnold; Hübl, Wolfgang; Spada, Stefano; Müldür, Ercan; Schlangen, Karin; Heintel, Daniel; Rocci, Alberto; Weißmann, Adalbert; Fritz, Veronique; Willheim, Martin; Zojer, Niklas; Palumbo, Antonio; Ludwig, Heinz

    2017-03-01

    Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the possibility that cell populations in the bone marrow (BM) microenvironment could serve as biomarkers. We therefore analysed gene expression levels of six IMiD target genes in whole BM samples of 44 myeloma patients treated with lenalidomide-dexamethasone. Expression of CRBN (R = 0.30, P = .05), IKZF1 (R = 0.31, P = .04), IRF4 (R = 0.38, P = .01), MCT-1 (R = 0.30, P = .05), and CD147 (R = 0.38, P = .01), but not IKZF3 (R = -0.15, P = .34), was significantly associated with response. Interestingly, IKZF1 expression was elevated in BM environmental cells and thus selected for further investigation by multicolor flow cytometry. High IKAROS protein levels in total BM mononuclear cells (median OS 83.4 vs. 32.2 months, P = .02), CD19(+) B cells (median OS 71.1 vs. 32.2 months, P = .05), CD3(+) CD8(+) T cells (median OS 83.4 vs 19.0 months, P = .008) as well as monocytes (median OS 53.9 vs 18.0 months, P = .009) were associated with superior overall survival (OS). In contrast, IKAROS protein expression in MM cells was not predictive for OS. Our data therefore corroborate the central role of immune cells for the clinical activity of IMiDs and built the groundwork for prospective analysis of IKAROS protein levels in distinct cell populations as a potential biomarker for IMiD based therapies.

  7. 153Sm-EDTMP治療肺癌多發性骨轉移的臨床應用78例%Clinical applications of 153 Sm-EDTMP in treatment of multiple bone metastases in 78 patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    肖國有; 李黨生; 梁藝華; 姚新娟

    2001-01-01

    Objective To evaluate the effect of 153Sm-EDTMP in treating patients with lung cancer and multiple bone metastases. Methods A dose of 18.5~25.9MBq/Kg ~Sm-EDTMP was administered once a month to each patient through vein injection according to disease severity and body weight. 3 injections made up one therapy cycle. Results Pain relieves were obtained in 65 patients, with an effective rate of 83.3%. Pain relief of grade Ⅰ was observed in 19 patients (24.3%), grade Ⅱ in 46 patients (59%) and grade Ⅲ in 13 patients (16.7%0),respectively. Lesions of bone metastases disappeared or shrunk in 9 patients, with a positive rate of 11.5 %. which included 3 cases of grade I and 6 cases of grade Ⅱ , respectively. Better effects were obtained in adenocarcinoma and squamous carcinoma than in small cell lung cancer. Conclusion 153Sm-EDTMP is safe and effective in treating patients with lung cancer and multiple bone metastases.

  8. Correlation between absence of bone remodeling compartment canopies, reversal phase arrest, and deficient bone formation in post-menopausal osteoporosis

    DEFF Research Database (Denmark)

    Levin Andersen, Thomas; Hauge, Ellen M; Rolighed, Lars;

    2014-01-01

    Bone remodeling compartments (BRCs) were recently recognized to be present in patients with primary hyperparathyroidism and critical for bone reconstruction in multiple myeloma and endogenous Cushing's syndrome. The BRCs are outlined by a cellular canopy separating the bone remodeling events...

  9. Estimation of the added value of 99mTc-HMPAO labelled white blood cells scintigraphy for the diagnosis of infectious foci.

    Science.gov (United States)

    Malherbe, Cécile; Dupont, Anne-Claire; Maia, Serge; Venel, Yann; Erra, Benoit; Santiago-Ribeiro, Maria-Joao; Arlicot, Nicolas

    2017-05-03

    Leucocytes Scintigraphy (LS) is an in vivo imaging technique investigating infectious foci, performed in our nuclear medicine department after a 99mTc-Bisphophonates Bone Scintigraphy (BS) or an 18F-FDG-PET, in osteoarticular or vascular localisations, respectively. The aim of this study was to reassert the relevance of LS in the diagnostic of occult infections and its impact in therapeutic management. A 45-months retrospective study (2012-2015), including 34 patients, was conducted. Patients who underwent LS were identified and classified according to the location of the suspected infection and the feature of first-line imaging exploration. The final diagnosis (infected or not-infect lesion) was established regarding patients' follow- up care, including clinical, biological biomarkers and therapeutic interventions. Sensitivity and specificity were calculated for each imaging modality. LS were conducted for exploration of joint prosthesis(14), vascular prosthesis(7), bone infection or osteitis(8), algoneurodystrophia(2), symphisis infection(1), acute infection on chronicle inflammation(1) and cancer(1). All patients underwent a previous imaging exploration: BS (20 cases-59%), 18FDG-PET (10 cases- 29%), or another exploration (4 cases-12%). The sensitivity and specificity of BS were 67% and 36%, respectively, and 100% and 50% for 18FDG-PET, evidencing the lack of specificity of these approaches. Fourteen LS were positive (41%), with sensitivity, specificity and diagnostic accuracy of 85%, 86% and 85%, respectively. Despite a long, delicate, and costly radiopharmaceutical and nuclear imaging process, the high specificity of LS supports its qualitative added value in the diagnosis of infectious foci, by improving clinical and therapeutic patient's outcomes.

  10. 多发伤与多发骨关节损伤的诊治进展%Research progress in diagnosis and treatment of polytrauma and multiple bone joint injury

    Institute of Scientific and Technical Information of China (English)

    金鸿宾

    2005-01-01

    多发伤(multiple injuries or polytrauma)是指同一致伤因素所致2个或2个以上解剖部位的严重损伤。多发骨关节损伤(multiple bone and ioint injury)又常称为多发骨折(poly fractures)或多肢体骨关节损伤(multiple extremity injury,MEI)。严格地讲,多肢体骨关节损伤系指2个以上的上、下肢长管状骨折及关节损伤,含脱位、骨与软骨损伤、

  11. Multiple annular linear diffractive axicons.

    Science.gov (United States)

    Bialic, Emilie; de la Tocnaye, Jean-Louis de Bougrenet

    2011-04-01

    We propose a chromatic analysis of multiple annular linear diffractive axicons. Large aperture axicons are optical devices providing achromatic nondiffracting beams, with an extended depth of focus, when illuminated by a white light source, due to chromatic foci superimposition. Annular apertures introduce chromatic foci separation, and because chromatic aberrations result in focal segment axial shifts, polychromatic imaging properties are partially lost. We investigate here various design parameters that can be used to achieve color splitting, filtering, and combining using these properties. In order to improve the low-power efficiency of a single annular axicon, we suggest a spatial multiplexing of concentric annular axicons with different sizes and periods we call multiple annular aperture diffractive axicons (MALDAs). These are chosen to maintain focal depths while enabling color imaging with sufficient diffraction efficiency. Illustrations are given for binary phase diffractive axicons, considering technical aspects such as grating design wavelength and phase dependence due to the grating thickness.

  12. A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells

    Directory of Open Access Journals (Sweden)

    Huber Peter E

    2011-02-01

    Full Text Available Abstract Background The protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target, DNA double-strand break (DSB formation and rejoining, apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2. Methods MRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB, or mock-treated, 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis (PFGE as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry, survival was quantified by clonogenic assay. Results TBB treatment did not affect initial DNA fragmention (PFGE; up to 80 Gy or foci formation (1 Gy. While DNA fragment rejoining (PFGE was not inhibited by the drug, TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions (monotherapies or combination, but TBB treatment at this moderately toxic concentration of 20 μM (about 40% survival enhanced radiation-induced cell killing in the clonogenic assay. Conclusions The data imply a role of CK2 in gamma-H2AX dephosporylation, most likely through its known ability to stimulate PP2A phosphatase, rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from interference with an apoptosis suppression function of CK2 in these cells but could reflect inhibitor-induced uncoupling of DNA damage response decay from break ligation.

  13. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    DEFF Research Database (Denmark)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels

    2010-01-01

    OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients recei...

  14. Follow-up of bone lesions in an experimental multiple myeloma mouse model: Description of an in vivo technique using radiography dedicated for mammography

    NARCIS (Netherlands)

    Vanderkerken, K.; Goes, E.; Raeve, H. de; Radl, J.; Camp, B. van

    1996-01-01

    The evolution of bone lesions in transplantable C57BL/KaLwRij 5T mouse myeloma (MM) has been followed in vivo. Mice were anaesthetised and a radiograph of the pelvis and hind legs was performed by a radiograph dedicated for mammography. This is the first description of an in vivo technique under

  15. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  16. Domestic animals as potential reservoir hosts of Trypanosoma brucei gambiense in sleeping sickness foci in Cameroon

    Directory of Open Access Journals (Sweden)

    Njiokou F.

    2010-03-01

    Full Text Available An explanation of the endemic nature and/or the resurgence of Human African Trypanosomiasis (HAT in the historic foci in West and Central Africa may be the existence of an animal reservoir. In some HAT foci, pigs were found infected by Trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. This study aims to determine the prevalence of T. b. gambiense in domestic animal species (goat, sheep, pig and dog commonly found in the four active HAT foci in Cameroon (Bipindi, Fontem, Campo and Doumé. Blood samples were collected from 307 pigs, 264 goats, 267 sheep and 37 dogs and used for parasitological (QBC, immunological (LiTat 1.3 CATT and molecular (PCR analyses. QBC detected trypanosomes in 3.88 % domestic animals while 22.7 % were sero-positive with LiTat 1.3 CATT tests. Of the 875 animals analysed, 174 (19.88 % harboured T. brucei s.l. DNA, found in each of the four types of animal and in the four localities. The infection rate significantly differed among the animal species (p < 0.0001 and localities (p < 0.0001. The PCR also revealed T. b. gambiense group 1 DNA in 27 (3.08 % domestic animals. The specific infection rates were as follows: sheep (6.74 %, goats (3.08 %, pigs (0.32 % and dogs (0 %. T. b. gambiense was found in 8 (3.92 % animals from Bipindi, 15 (4.83 % from Campo, 4 (2.59 % from Fontem-Center and none from Doumé. The infection rates significantly differed between the localities, and correlated with the intensity of HAT transmission in the foci.

  17. CDC25B overexpression stabilises centrin 2 and promotes the formation of excess centriolar foci.

    Directory of Open Access Journals (Sweden)

    Rose Boutros

    Full Text Available CDK-cyclin complexes regulate centriole duplication and microtubule nucleation at specific cell cycle stages, although their exact roles in these processes remain unclear. As the activities of CDK-cyclins are themselves positively regulated by CDC25 phosphatases, we investigated the role of centrosomal CDC25B during interphase. We report that overexpression of CDC25B, as is commonly found in human cancer, results in a significant increase in centrin 2 at the centrosomes of interphase cells. Conversely, CDC25B depletion causes a loss of centrin 2 from the centrosome, which can be rescued by treatment with the proteasome inhibitor MG132. CDC25B overexpression also promotes the formation of excess centrin 2 "foci". These foci can accumulate other centrosome proteins, including γ-tubulin and PCM-1, and can function as microtubule organising centres, indicating that these represent functional centrosomes. Formation of centrin 2 foci can be blocked by specific inhibition of CDK2 but not CDK1. CDK2-mediated phosphorylation of Monopolar spindle 1 (Mps1 at the G1/S transition is essential for the initiation of centrosome duplication, and Mps1 is reported to phosphorylate centrin 2. Overexpression of wild-type or non-degradable Mps1 exacerbated the formation of excess centrin 2 foci induced by CDC25B overexpression, while kinase-dead Mps1 has a protective effect. Together, our data suggest that CDC25B, through activation of a centrosomal pool of CDK2, stabilises the local pool of Mps1 which in turn regulates the level of centrin 2 at the centrosome. Overexpression of CDC25B may therefore contribute to tumourigenesis by perturbing the natural turnover of centrosome proteins such as Mps1 and centrin 2, thus resulting in the de novo assembly of extra-numerary centrosomes and potentiating chromosome instability.

  18. Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer

    OpenAIRE

    Jay Morris; Michael J. Wargovich; Brown, Vondina R.

    2010-01-01

    Aberrant crypt foci (ACF) are one of the earliest histopathological manifestations of colon cancer. In this review, we critically present the molecular, cellular, histopathological, and chemopreventive evidence that ACF are relevant biomarkers for colon cancer. The laboratory and clinical evidence are highly suggestive that ACF are in the pathway leading to colon cancer, but not all ACF will do so. The possible fate and outcome of ACF in the progression toward colon cancer may be dependent on...

  19. Sanation of carious and periapical foci in young athletes with impairment of cardiovascular adaptation

    Directory of Open Access Journals (Sweden)

    I. I. Belyaev

    2014-01-01

    Full Text Available The aim of this study was to evaluate the impact of sanation of oral cavity in young athletes on the course of adaptation of the cardiovascular system to the condition of sports activities. According to the research results, it was revealed that the optimal period for sanation of periapical odontogenic foci in athletes with clinical signs of impairment (dysfunction of cardiovascular system adaptation to exercise stress was a preparatory training period, while carious lesion sanation required preparatory or postcompetition periods.

  20. 99 Tcm-MDP whole body bone imaging in patients with multiple osteochondroma%多发性骨软骨瘤病的99Tcm-MDP全身骨显像分析

    Institute of Scientific and Technical Information of China (English)

    张连娜; 冯瑾; 陈瑞玲; 何海燕; 杨芳

    2013-01-01

    Objective To investigate the usefulness of 99mTc-MDP whole body bone scintigraphy (WBBS) in patients with multiple osteochondroma.Methods 99mTc-MDP WBBS was performed in 62 patients with multiple osteochondroma.The typical scintigraphic manifestations of multiple osteochondroma were summarized and compared to other radiological imaging data.Results Among 62 patients,100% of cases were associated with Painless bone mass; 17.7% accompanied by joint dysfunction,53.2% had a family history.Bone scintigraphy found that the most common location of exostosis was juxta-epiphyscal regions of the long bones,no exostosis was found in skull.In all lesions,one grade of uptake accounted for 7.9% of all lesions (24/305),tone grade of uptake lesions accounted for 34.1 of all lesions (104/305),3 uptake lesions accounted for 40.0% of all lesions (122/305),four pickup lesions accounted for all lesions of 18% (55/305).Conclusion Multiple osteochondromatosis showed irregular various radioactive concentration in end of long bones,99mTc-MDP bone scintigraphy,which combined with clinical and radiological data,can be used to diagnose,differentiate,and localize the insidious lesion and evaluate the tumor malignant transformation in patients with multiple osteochondroma.%目的 分析多发性骨软骨瘤病的99mTc-MDP全身骨显像的影像特点,评价骨显像在多发性骨软骨瘤病中的应用价值.方法 回顾分析62例确诊为多发性骨软骨瘤病患者的临床、骨显像及其他影像学资料,总结多发性骨软骨瘤病的骨显像特点,并与其他影像学结果进行比较.结果 62例患者中,100%在身体不同地方发现无痛性骨性包块,其中17.7%伴有关节功能障碍,53.2%有家族史.骨显像发现全身骨骼受累最多的部位前三位分别为胫骨近端17.4%、股骨远端17.0%、股骨近端16.4%.受累最少的部位为颅骨0%.在所有病灶中,1级摄取病灶占全部病灶的7.9%(24/305)、2级

  1. Archival bone marrow samples

    DEFF Research Database (Denmark)

    Lund, Bendik; Najmi, Laeya A; Wesolowska-Andersen, Agata;

    2015-01-01

    AB Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole...... with samples stored for 4 to 10 years. Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In conclusion, archival bone marrow samples are suitable for DNA extraction and multiple marker analysis, but WGA was less successful, especially when longer fragments were analyzed. Multiple SNP...

  2. Rapid identification of paragonimiasis foci by lay informants in Lao People's Democratic Republic.

    Directory of Open Access Journals (Sweden)

    Peter Odermatt

    Full Text Available BACKGROUND: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases. METHODOLOGY/PRINCIPAL FINDINGS: The study was carried out in an endemic area of Lao People's Democratic Republic. Leaders of 49 remote villages in northern Vientiane Province were asked to notify suspected paragonimiasis patients using a four-item questionnaire sent through administrative channels: persons responding positively for having chronic cough (more than 3 weeks and/or blood in sputum with or without fever. We validated the village leaders' reports in ten representative villages with a door-to-door survey. We examined three sputa of suspected patients for the presence of Paragonimus eggs and acid fast bacilli. 91.8% of village leaders participated and notified a total of 220 suspected patients; 76.2% were eventually confirmed; an additional 138 suspected cases were found in the survey. Sensitivity of village leaders' notice for "chronic cough" and "blood in sputum" was 100%; "blood in sputum" alone reached a sensitivity of 85.7%. SIGNIFICANCE: Our approach led to the identification of three previously unknown foci of transmission. A rapid and simple lay-informant questionnaire approach is a promising low-cost community diagnostic tool of paragonimiasis control programs.

  3. Evaluation of three-dimensional distribution of foci of diffuse lung diseases with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Masamitsu [Nagoya City Univ. (Japan). Medical School

    1998-11-01

    Three-dimensional distribution of foci of diffuse lung disease was evaluated by CT image, and it was examined whether each lung disease could be diagnosed by different distribution. Subjects were 120 cases (idiopathic interstitial pneumonia 15 cases, sarcoidosis 23 cases, miliary tuberculosis 10 cases, diffuse panbronchiolitis 7 cases, chronic pulmonary emphysema 6 cases, pulmonary metastasis 9 cases, SLE 6 cases, PSS 8 cases, dermatomyositis (DM) 6 cases, RA 7 cases, SjS 9 cases and others 14 cases). CT image was obtained from apex to base of lung with 10 mm gapless. The image was divided into three parts in both head-tail direction and back-front direction, and two parts in cortex medulla direction, and the ratio of foci to whole in each part was evaluated in five phases, and the part with the highest ratio was determined as the predominant side. In idiopathic interstitial pneumonia, sarcoidosis, miliary tuberculosis, diffuse panbronchiolitis, chronic pulmonary emphysema, pulmonary metastasis, PSS and DM, the predominant side was confirmed, respectively, and usefulness of differential diagnosis was recognized. Constant distribution wasn't recognized in SLE, RA and SjS, because the state of disease was not always same in the foci of these diseases. (K.H.)

  4. PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rudolph, Jeanette Heede [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Jakob, Burkhard [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Fink, Daniela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Tobias, Frank [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany); Blattner, Christine [Karlsruhe Inst. of Technology (KIT) (Germany). Inst. of Toxicology and Genetics; Taucher-Scholz, Gisela [GSI-Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany)

    2012-03-26

    The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in response to DNA damage and inhibits DNA replication through its direct interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin-dependent kinase complexes. Previously, we reported that in response to densely ionizing radiation CDKN1A rapidly is recruited to the sites of particle traversal, and that CDKN1A foci formation in response to heavy ions is independent of its transactivation by TP53. In this paper, we show that exposure of normal human fibroblasts to X-rays or to H2O2 also induces nuclear accumulations of CDKN1A. We find that CDKN1A foci formation in response to radiation damage is dependent on its dephosphorylation and on its direct physical interaction with PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed-PCNA show rapid recruitment of both proteins into foci after radiation damage. Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A compared to PCNA, which is best described by bi-exponential curve fitting, taking the preceding binding of PCNA to DNA into account. Finally, we propose a regulatory role for CDKN1A in mediating PCNA function after radiation damage, and provide evidence that this role is distinct from its involvement in nucleotide excision repair and unrelated to double-strand break repair.

  5. Enhancing effects of mustard oil on preneoplastic hepatic foci development in Wistar rats.

    Science.gov (United States)

    Shukla, Yogeshwer; Arora, Annu

    2003-02-01

    Dietary habits are known to be the major contributory factor in the development of cancer. Mustard oil, which is extensively used in India and elsewhere as a flying and cooking medium, is reported to induce an inflammatory response. The development of altered hepatic foci is an early carcinogenic change in rat liver in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. In the present study, the development of preneoplastic lesions was observed following administration of mustard oil (0.5 mL/day for 8 weeks) in DEN-initiated and partially hepatomized Wistar rats. A significant decrease in the relative and absolute liver weight of mustard oil-exposed rats was recorded. The results revealed a significant increase in the number and area of placental glutathione-S-transferase (GST-P) and gamma-glutamyl transpeptidase (GGT)-positive foci in mustard oil-administered animals. The GST-P- and GGT-positive foci were more prominent in the animals given boiled (up to 300 degrees C for 3 hours) mustard oil in comparison to the animals given fresh mustard oil. These results indicate the possible tumourigenic risk associated with mustard oil consumption.

  6. Lack of promoting activity of four pesticides on induction of preneoplastic liver cell foci in rats.

    Science.gov (United States)

    Kato, T; Ogiso, T; Kato, K; Sano, M; Hasegawa, R; Shirai, T; Ito, N

    1995-01-01

    Four pesticides were examined for hepatopromoting activity using a medium-term bioassay based upon induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver. Male F344 rats were initially injected with diethylnitrosamine (DEN; 200 mg/kg body weight) intraperitoneally and 2 weeks later were treated with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN; 75 and 150 ppm), diazinon (500 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. All of the pesticides gave negative results, the numbers and areas of GST-P positive foci not exceeding the control values for animals given DEN alone. Indeed, a significant reduction of foci development was seen for EPN (75 ppm). These findings provide experimental evidence that the presently examined four pesticides do not have hepatocarcinogenic potential in rats.

  7. Bone marrow aspiration

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Krzysztof H. Włodarski

    2012-10-01

    Full Text Available The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically
    induced bone evaluated 4–42 weeks post implantation of demineralized murine incisors was estimated by histological
    analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,
    the proportion of nuclear cells vs. adipocytes was ascertained. The percentage of adipocytes in marrow
    increases over time. Such an effect, the replacement of myelopoietic marrow by adipogenic (yellow marrow
    and the resorption of induced bone, is observed in human osteoporosis. A decline in the non-adipogenic cell
    compartments of bone marrow accompanying induced bone begins in the fourth week of induction, gradually
    progresses until the 26th week, and does not change after that. The luminosity, a parameter used in image analysis
    and proportional to the number of nuclear cells, was 124 ± 3 in hematopoietic femoral bone marrow, and
    that of bone marrow of the induced bone was of a similar value (117 ± 8 in the fourth week. An evident decline
    in luminosity of bone marrow filling the foci of heterotopic bone was observed in samples taken at nine weeks
    (82 ± 20. This process progressed until the 26th week, reaching a luminosity of 70 ± 21. At the 42nd week, the
    luminosity remained at the same level (71 ± 27. This indicates that the replacement of hematopoietic bone
    marrow of heterotopically induced bone by unilocular adipocytes begins relatively early (the fourth week and is
    persistent.The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically
    induced bone evaluated 4–42 weeks post implantation of demineralized murine incisors was estimated by histological
    analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,
    the proportion of nuclear cells vs

  9. AFSC/RACE/EcoFOCI - Ichthyoplankton data collected in support of FOCI assessment surveys and ecosystem observations in the Bering, Beaufort, and Chukchi Seas and the Gulf of Alaska 1972 to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The dataset contains records of fish eggs and larvae collected during FOCI assessment surveys. Records include all data pertinent to identify where specimens were...

  10. Development of an in vitro three dimensional loading-measurement system for long bone fixation under multiple loading conditions: a technical description

    Directory of Open Access Journals (Sweden)

    Wilson David A

    2007-11-01

    Full Text Available Abstract The purpose of this investigation was to design and verify the capabilities of an in vitro loading-measurement system that mimics in vivo unconstrained three dimensional (3D relative motion between long bone ends, applies uniform load components over the entire length of a test specimen, and measures 3D relative motion between test segment ends to directly determine test segment construct stiffness free of errors due to potting-fixture-test machine finite stiffness. Intact equine cadaveric radius bones, which were subsequently osteotomized/ostectomized and instrumented with bone plates were subjected to non-destructive axial, torsion, and 4-point bending loads through fixtures designed to allow unconstrained components of non-load associated 3D relative motion between radius ends. 3D relative motion between ends of a 50 mm long test segment was measured by an infrared optical tracking system to directly determine its stiffness. Each specimen was then loaded to ultimate failure in either torsion or bending. Cortical bone cross-section diameters and published bone biomechanical properties were substituted into classical mechanics equations to predict the intact test segment theoretical stiffness for comparison and thus loading-measurement system verification. Intact measured stiffness values were the same order of magnitude as theoretically predicted. The primary component of relative motion between ends of the test segment corresponded to that of the applied load with the other 3D components being evident and consistent in relative magnitude and direction for unconstrained loading of an unsymmetrical double plate oblique fracture configuration. Bone failure configurations were reproducible and consistent with theoretically predicted. The 3D loading-measurement system designed: a mimics unconstrained relative 3D motion between radius ends that occurs in clinical situations, b applies uniform compression, torsion, and 4-point bending loads

  11. Treatment of multiple traumatized anterior teeth associated with an alveolar bone fracture in a 20-year-old patient: a 3-year follow up

    OpenAIRE

    2014-01-01

    Intrusive luxation is a type of recognizable luxation injury represented by a deeper axial displacement of the tooth toward the alveolar bone. Treatment strategies include waiting for the tooth to return to its position, immediate surgical repositioning, and repositioning through dental traction by orthodontic devices. The aim of this case report was to present the management of severe dental trauma and later restoration following IADT. A 20-year-old patient was presented after fainting at ho...

  12. AFSC/RACE/EcoFOCI: 2010 BEST and BSIERP Study 1WE10/WE10-08

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecosystem & Fisheries-Oceanography Coordinated Investigations (Eco-FOCI) is an effort by National Oceanic and Atmospheric Administration (NOAA) and associated...

  13. Imaging Features that Discriminate between Foci Induced by High-and Low-LET Radiation in Human Fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano,Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

    2006-10-08

    In this study, we investigated the formation ofradiation-induced foci in normal human fibroblasts exposed to X rays or130 keV/mum nitrogen ions using antibodies to phosphorylated proteinkinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantifythe immunofluorescence of radiation-induced foci. The size ofradiation-induced foci increased for both proteins over a 2-h periodafter nitrogen-ion irradiation, while the size of radiation-induced focidid not change after exposure to low-LET radiation. The number ofradiation-induced ATMp foci showed a more rapid rise and greaterfrequency after X-ray exposure and was resolved more rapidly such thatthe frequency of radiation-induced foci decreased by 90 percent comparedto 60 percent after exposure to high-LET radiation 2 h after 30 cGy. Incontrast, the kinetics of radiation-induced gamma-H2AX focus formationwas similar for high- and low-LET radiation in that it reached a plateauearly and remained constant for up to 2 h. High-resolution 3D images ofradiation-induced gamma-H2AX foci and dosimetry computation suggest thatmultiple double-strand breaks from nitrogen ions are encompassed withinlarge nuclear domains of 4.4 Mbp. Our work shows that the size andfrequency of radiation-induced foci vary as a function of radiationquality, dose, time and protein target. Thus, even though double-strandbreaks and radiation-induced foci are correlated, the dynamic nature ofboth contradicts their accepted equivalence for low doses of differentradiation qualities.

  14. p53 binding protein 1 foci as a biomarker of DNA double strand breaks induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, C.K.M.; Wong, M.Y.P.; Lam, R.K.K.; Ho, J.P.Y. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chiu, S.K. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2011-12-21

    Foci of p53 binding protein 1 (53 BP1) have been used as a biomarker of DNA double-strand breaks (DSBs) in cells induced by ionizing radiations. 53 BP1 was shown to relocalize into foci shortly after irradiation, with the number of foci closely paralleling the number of DNA DSBs. However, consensus on criteria in terms of the numbers of 53 BP1 foci to define cells damaged by direct irradiation or by bystander signals has not been reached, which is partly due to the presence of 53 BP1 also in normal cells. The objective of the present work was to study the changes in the distribution of cells with different numbers of 53 BP1 foci in a cell population after low-dose ionizing irradiation (<0.1 Gy) provided by alpha particles, with a view to propose feasible criteria for defining cells damaged by direct irradiation or by bystander signals. It was proposed that the change in the percentage of cells with 1-3 foci should be used for such purposes. The underlying reasons were discussed.

  15. Intraprostatic locations of tumor foci of higher grade missed by diagnostic prostate biopsy among potential candidates for active surveillance

    Science.gov (United States)

    Kim, Kwangmo; Lee, Jung Keun; Choe, Gheeyoung; Hong, Sung Kyu

    2016-01-01

    To establish optimal biopsy scheme for selection of candidates for active surveillance (AS) among prostate cancer (PCa) patients, information on topographical distribution of tumor foci of higher grade missed by contemporary biopsy amongst potential candidates of AS would certainly be useful. Thus we analyzed topographic distribution of tumor foci by examining prostatectomy specimens in 444 patients who underwent radical prostatectomy for low risk PCa. Anterior and posterior prostate areas were demarcated by a horizontal line drawn at midpoint of prostatic urethra. Among 444 subjects, patients with upgrading showed relatively higher prevalence of index tumor foci in anterior prostate than those without upgrading, though not reaching statistical significance (p = 0.252). Meanwhile, among 135 (30.4%) patients with very low risk PCa, patients with upgrading showed significantly higher prevalence of index tumor foci in anterior prostate than those without upgrading (52.2% vs 33.8%; p = 0.031). In conclusions, tumor foci of higher grade missed by diagnostic biopsy were mostly located in anterior prostate among very low risk PCa patients. Such finding would be concrete evidence to support the notion that more efforts are needed to increase accuracy in detecting tumor foci in anterior prostate among potential candidates for AS. PMID:27827421

  16. 99m Tc-MDP whole body bone imaging in patients with multiple osteochondroma%遗传性多发性骨软骨瘤病的全身骨扫描特点

    Institute of Scientific and Technical Information of China (English)

    张连娜; 冯瑾; 陈瑞玲; 何海燕; 杨芳

    2014-01-01

    目的:分析遗传性多发性骨软骨瘤(HME)的99m Tc - MDP 全身骨显像的影像特点,评价骨显像在 HME 中的应用价值。方法分析74例确诊为 HME 患者的临床、骨显像资料,总结 HME 的骨显像特点。结果74例患者中,肿瘤好发部位位于长骨的干骺端,颅面骨未见发现,主要表现为长骨干骺端骨质增粗,以膝关节周围表现最为明显;在所有病灶中,未见放射性摄取减低病灶(0级)。全身骨显像共显示371个病灶,其中1级摄取病灶占全部病灶的8.6%(32/371),2级摄取病灶占全部病灶的34.2%(127/371),3级摄取病灶占全部病灶的39.6%(147/371),4级摄取病灶占全部病灶的17.5%(65/371)。结论 HME 的全身骨显像表现为长骨末端异常的、不规则的、多处的放射性浓聚,结合临床及其他影像学资料,99m Tc - MDP 全身骨显像可用于 HME 患者的诊断与鉴别诊断、随访以及肿瘤恶变的评价。%Objective To investigate the usefulness of 99Tcm - MDP whole body bone scintigraphy(WBBS)in patients with Hereditary multiple exostoses HME. Methods 99m Tc - MDP WBBS was performed in 74 patients with HME. The typical scintigraphic manifestations of He-reditary multiple exostoses HME were summarized. Results Bone scintigraphy found that the most common location of exostosis was juxta -epiphyscal regions of the long bones among 74 patients,showed bone thickening. The change around the knee joint was the most obvious. No exos-tosis was found in skull. In all lesions,1 grade of uptake accounted for8. 6% of all lesions(32 / 371),2 grade of uptake lesions accounted for 34. 2 of all lesions(127 / 371),3 uptake lesions accounted for 39. 6% of all lesions(147 / 371),four pickup lesions account for all lesions of 17. 5%(65 / 371). Conclusion Hereditary multiple exostoses showed irregular various radioactive concentration in end of long bones,99Tcm - MDP bone scintigraphy which combined

  17. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M

    2014-01-01

    There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...... in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival....

  18. Acidosis, hypoxia and bone.

    Science.gov (United States)

    Arnett, Timothy R

    2010-11-01

    Bone homeostasis is profoundly affected by local pH and oxygen tension. It has long been recognised that the skeleton contains a large reserve of alkaline mineral (hydroxyapatite), which is ultimately available to neutralise metabolic H(+) if acid-base balance is not maintained within narrow limits. Bone cells are extremely sensitive to the direct effects of pH: acidosis inhibits mineral deposition by osteoblasts but it activates osteoclasts to resorb bone and other mineralised tissues. These reciprocal responses act to maximise the availability of OH(-) ions from hydroxyapatite in solution, where they can buffer excess H(+). The mechanisms by which bone cells sense small pH changes are likely to be complex, involving ion channels and receptors in the cell membrane, as well as direct intracellular effects. The importance of oxygen tension in the skeleton has also long been known. Recent work shows that hypoxia blocks the growth and differentiation of osteoblasts (and thus bone formation), whilst strongly stimulating osteoclast formation (and thus bone resorption). Surprisingly, the resorptive function of osteoclasts is unimpaired in hypoxia. In vivo, tissue hypoxia is usually accompanied by acidosis due to reduced vascular perfusion and increased glycolytic metabolism. Thus, disruption of the blood supply can engender a multiple negative impact on bone via the direct actions of reduced pO(2) and pH on bone cells. These observations may contribute to our understanding of the bone disturbances that occur in numerous settings, including ageing, inflammation, fractures, tumours, anaemias, kidney disease, diabetes, respiratory disease and smoking.

  19. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Telfer, Sandra; Rajerison, Minoarisoa; Ranjalahy, Michel A; Andriamiarimanana, Fehivola; Rahaingosoamamitiana, Corinne; Rahalison, Lila; Jambou, Ronan

    2012-01-01

    Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  20. Assembly and function of DNA double-strand break repair foci in mammalian cells

    DEFF Research Database (Denmark)

    Bekker-Jensen, Simon; Mailand, Niels

    2010-01-01

    phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance...... of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures....

  1. Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

    Science.gov (United States)

    Barash, N. R.; Nosala, C.; Pham, J. K.; McInally, S. G.; Gourguechon, S.; McCarthy-Sinclair, B.

    2017-01-01

    ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand

  2. Aesthetic Multiple-Toe Reconstruction With Combined Iliac Bone Graft and Wraparound Free Anterolateral Thigh Flap-A Case Report and Literature Review.

    Science.gov (United States)

    Kwon, Soo-Ha; Lao, William; Yen, Cheng-I; Lin, Yu-Te; Wu, Katie Pei-Hsuan; Chang, Tommy Nai-Jen

    2017-03-01

    Compared with upper extremity injuries, toe amputations and their replantations are rare because of the difficulty of their relatively thinner soft tissue envelope. Consequently, fewer reconstructive options are available for toes and they are rarely reported in the literature. In this study, we reported a case of right third to fifth toe amputations and their subsequent reconstruction with iliac bone grafts and a free anterolateral thigh flap. After serial debulking and division procedures, 3 toes were divided successfully. Ten months after the initial operation, the patient regained pain-free functional ambulation despite some bone resorption noted on follow-up radiographs. The patient showed high satisfaction on her new toes in terms of aesthetical and functional outcomes. She was able to stand for over 30 minutes without pain. At the 2-year follow-up, the Foot Function Index was 18.3%. Although toe reconstruction is frequently considered unnecessary because of its relative high demand of surgical techniques and little gain on gait; nonetheless, in selected cases, toe reconstruction may still be beneficial if the metatarsophalangeal joints were intact and there is a strong individual desire for aesthetical restoration.

  3. Androgen and bone mass in men

    Institute of Scientific and Technical Information of China (English)

    AnnieW.C.Kung

    2003-01-01

    Androgens have multiple actions on the skeleton throughout life. Androgens promote skeletal growth and accumulation of minerals during puberty and adolescence and stimulate osteoblast but suppress osteoclast function,activity and lifespan through complex mechanisms. Also androgens increase periosteal bone apposition, resulting in larger bone size and thicker cortical bone in men. There is convincing evidence to show that aromatization to estrogens was an important pathway for mediating the action of testosterone on bone physiology. Estrogen is probably the dominant sex steroid regulating bone resorption in men, but both testosterone and estrogen are important in maintaining bone formation. ( Asian J Androl 2003 Jun; 5: 148-154)

  4. Bone disease and HIV infection.

    Science.gov (United States)

    Amorosa, Valerianna; Tebas, Pablo

    2006-01-01

    The high prevalence of bone demineralization among human immunodeficiency virus (HIV)-infected patients in the current therapeutic era has been described in multiple studies, sounding the alarm that we may expect an epidemic of fragility fractures in the future. However, despite noting high overall prevalences of osteopenia and osteoporosis, recent longitudinal studies that we review here have generally not observed accelerated bone loss during antiretroviral therapy beyond the initial period after treatment initiation. We discuss the continued progress toward understanding the mechanisms of HIV-associated bone loss, particularly the effects of HIV infection, antiretroviral therapy, and host immune factors on bone turnover. We summarize results of clinical trials published in the past year that studied the safety and efficacy of treatment of bone loss in HIV-infected patients and provide provisional opinions about who should be considered for bone disease screening and treatment.

  5. Mangiferin reduces the inhibition of chondrogenic differentiation by IL-1β in mesenchymal stem cells from subchondral bone and targets multiple aspects of the Smad and SOX9 pathways.

    Science.gov (United States)

    Huh, Jeong-Eun; Koh, Pil-Seong; Seo, Byung-Kwan; Park, Yeon-Chul; Baek, Yong-Hyun; Lee, Jae-Dong; Park, Dong-Suk

    2014-09-11

    Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1β-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1β (IL-1β). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y-box (SRY-box) containing gene 9 (SOX9), type 2α1 collagen (Col2α1), cartilage link protein, and aggrecan. In IL-1β-stimulated MSCs, mangiferin significantly reversed the production of TGF-β, BMP-2, BMP-4, SOX9, Col2α1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1β-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2α1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.

  6. Mangiferin Reduces the Inhibition of Chondrogenic Differentiation by IL-1β in Mesenchymal Stem Cells from Subchondral Bone and Targets Multiple Aspects of the Smad and SOX9 Pathways

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2014-09-01

    Full Text Available Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1β-stimulated mesenchymal stem cells (MSCs from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1β (IL-1β. Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF-β, bone morphogenetic protein (BMP-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y–box (SRY-box containing gene 9 (SOX9, type 2α1 collagen (Col2α1, cartilage link protein, and aggrecan. In IL-1β-stimulated MSCs, mangiferin significantly reversed the production of TGF-β, BMP-2, BMP-4, SOX9, Col2α1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5. Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1β-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2α1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.

  7. Role of a Burr Hole and Calvarial Bone Marrow-Derived Stem Cells in the Ischemic Rat Brain: A Possible Mechanism for the Efficacy of Multiple Burr Hole Surgery in Moyamoya Disease

    Science.gov (United States)

    Nam, Taek-kyun; Park, Yong-sook; Kwon, Jeong-taik; Min, Byung-kook; Hwang, Sung-nam

    2015-01-01

    Objective This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). Methods Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. Results In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. Conclusion Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD. PMID:26539257

  8. Multiple osteochondromas

    Directory of Open Access Journals (Sweden)

    Bovée Judith VMG

    2008-02-01

    Full Text Available Abstract Multiple osteochondromas (MO is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1. Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular

  9. Schistosomiasis mansoni in areas of low transmission: epidemiological characterization of Venezuelan foci

    Directory of Open Access Journals (Sweden)

    Alarcón de Noya B

    2002-01-01

    Full Text Available Severe schistosomiasis is a rare event in Venezuela nowadays, after a successful national campaign by the Schistosomiasis Control Program. Unfortunately, this program has practically disappeared, and snail surveillance in field is not a priority, anymore. Thus, schistosomiasis has become a neglected disease in this country. However, surveys in different populations from the endemic area have shown particular epidemiological features described herein. In five communities we evaluated 2,175 persons and searched for the presence of Biomphalaria glabrata snails. Some markers were used for classifying schistosomiasis foci: mean age of the persons with Schistosoma mansoni eggs in the stools, serological tests, presence of B. glabrata snails, and intensity of infection. Places without B. glabrata snails and with few schistosomiasis cases were defined as "past transmission sites"; a site with abundant snails but few cases was defined as "potential risk"; "new transmission" foci were characterized by the presence of infected snails and young people passing eggs in the stools. A "re-emergent" focus has shared these last features, showing in addition a place where schistosomiasis had been reported before. Recent evidences of active transmission with the increasing dispersion of B. glabrata snails, point out the necessity for the re-establishment of the Schistosomiasis Control Program in Venezuela.

  10. The ability of two cooked food mutagens to induce aberrant crypt foci in mice

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1997-01-01

    The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet, In the present study two food-borne initiators, 2-amino-3-methyl-imidazo [4,5-f]quinoline (IQ) and 2......-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used, To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses, Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP, Two additional groups were given...... azoxymethane (AOM) (5 mg/kg body weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCI) (20 mg/kg body weight), respectively, one dose a week for two weeks, Animals were killed after four and 10 weeks, After four weeks only the mice dosed with IQ and PhIP had aberrant crypt foci, A much higher number...

  11. The Performance of Ictal Brain SPECT for Localizing Epileptogenic Foci in Temporal Lobe epilepsies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Sil; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon; Chang, Kee Hyun; Lee, Sang Kun; Chung, Chun Kee [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1995-06-15

    Anterior temporal lobectomy has become a widely used respective surgery in patients with medically intractable temporal lobe epilepsies. Prerequisites of this resection include the accurate localization of the epileptogenic focus and the determination that the proposed resection would not result in unacceptable postoperative memory or language deficits. The purpose of this study was to evaluate the performance of ictal SPECT compared to MRI findings for localization of epileptogenic foci in this group of patients. 11 patients who had been anterior temporal oral lobectomy were evaluated with ictal {sup 99m}Tc-HMPAO SPECT and MRI. MRI showed 8/11(73%) concordant lesion to the side of surgery and ictal SPECT also showed 8/11(73%) concordant hyperperfusion. In 3 cases with incorrect or nonlocalizing findings of MRI, ictal SPECT showed concordant hyperperfusion. In 2 cases confirmed by pre-resectional invasive EEG, MRI showed bilateral and contralateral lesion but ictal SPECT showed concordant hyperperfusion. 3 delayed injection of ictal SPECT showed discordant hyperperfusion. Thus, ictal SPECT was a useful method for localizing epileptogenic foci in temporal lobe epilepsies and appeared complementay to MRI.

  12. Characteristics of {gamma}-H2AX foci at DNA double-strand breaks sites

    Energy Technology Data Exchange (ETDEWEB)

    Pilch, D.R.; Sedelnikova, O.A.; Redon, C. [National Cancer Institute, National Institutes of Health, Lab. of Molecular Pharmacology, Bethesda, Maryland (United States); Celeste, A.; Nussenzweig, A. [National Cancer Institute, National Institutes of Health, Experimental Immunology Branch, Bethesda, Maryland (United States); Bonner, W.M. [National Cancer Institute, National Institutes of Health, Lab. of Molecular Pharmacology, Bethesda, Maryland (United States)

    2003-06-01

    Phosphorylated H2AX ({gamma}-H2AX) is essential to the efficient recognition and (or) repair of DNA double strand breaks (DSBs), and many molecules, often thousands, of H2AX become rapidly phosphorylated at the site of each nascent DSB. An antibody to {gamma}-H2AX reveals that this highly amplified process generates nuclear foci. The phosphorylation site is a serine four residues from the C-terminus which has been evolutionarily conserved in organisms from giardia intestinalis to humans. Mice and yeast lacking the conserved serine residue demonstrate a variety of defects in DNA DSB processing. H2AX{sup {delta}}{sup /{delta}} mice are smaller, sensitive to ionizing radiation, defective in class switch recombination and spermatogenesis while cells from the mice demonstrate substantially increased numbers of genomic defects. {gamma}-H2AX foci formation is a sensitive biological dosimeter and presents new and exciting opportunities to understand important biological processes, human diseases, and individual variations in radiation sensitivity. These potentialities demonstrate the importance of understanding the parameters and functions of {gamma}-H2AX formation. (author)

  13. An improved classification of foci for carcinogenicity testing by statistical descriptors.

    Science.gov (United States)

    Callegaro, Giulia; Stefanini, Federico Mattia; Colacci, Annamaria; Vaccari, Monica; Urani, Chiara

    2015-10-01

    Carcinogenesis is a multi-step process involving genetic alterations and non-genotoxic mechanisms. The in vitro cell transformation assay (CTA) is a promising tool for both genotoxic and non-genotoxic carcinogenesis. CTA relies on the ability of cells (e.g. BALB/c 3T3 mouse embryo fibroblasts) to develop a transformed phenotype after the treatment with suspected carcinogens. The classification of the transformed phenotype is based on coded morphological features, which are scored under a light microscope by trained experts. This procedure is time-consuming and somewhat prone to subjectivity. Herewith we provide a promising approach based on image analysis to support the scoring of malignant foci in BALB/c 3T3 CTA. The image analysis system is a quantitative approach, based on measuring features of malignant foci: dimension, multilayered growth, and invasivity into the surrounding monolayer of non-transformed cells. A logistic regression model was developed to estimate the probability for each focus to be transformed as a function of three statistical image descriptors. The estimated sensitivity of the derived classifier (untransformed against Type III) was 0.9, with an Area Under the Curve (AUC) value equal to 0.90 under the Receiver Operating Characteristics (ROC) curve.

  14. Effect of High-Dose Vitamin D3 Intake on Ambulation, Muscular Pain and Bone Mineral Density in a Woman with Multiple Sclerosis: A 10-Year Longitudinal Case Report

    Directory of Open Access Journals (Sweden)

    François Feron

    2012-10-01

    Full Text Available Mounting evidence correlate vitamin D3 (cholecalciferol supplementation or higher serum levels of vitamin D (25(OHD with a lower risk of developing multiple sclerosis (MS, reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who was diagnosed with MS in 1990. From 1980 to 2000, her ability to walk decreased from ~20 to 1 km per day. Since January 2001, a vitamin D3 supplement was ingested daily. The starting dose was 20 mcg (800 IU/day and escalated to 100 mcg (4000 IU/day in September 2004 and then to 150 mcg (6000 IU/day in December 2005. Vitamin D3 intake reduced muscular pain and improved ambulation from 1 (February 2000 to 14 km/day (February 2008. Vitamin D intake over 10 years caused no adverse effects: no hypercalcaemia, nephrolithiasis or hypercalciuria were observed. Bowel problems in MS may need to be addressed as they can cause malabsorption including calcium, which may increase serum PTH and 1,25(OH2D levels, as well as bone loss. We suggest that periodic assessment of vitamin D3, calcium and magnesium intake, bowel problems and the measurement of serum 25(OHD, PTH, Ca levels, UCa/Cr and bone health become part of the integral management of persons with MS.

  15. Treatment of multiple traumatized anterior teeth associated with an alveolar bone fracture in a 20-year-old patient: A 3-year follow up.

    Science.gov (United States)

    Faus-Matoses, Vicente; Martínez-Viñarta, María; Alegre-Domingo, Teresa; Faus-Matoses, Ignacio; Faus-Llácer, Vicente J

    2014-10-01

    Intrusive luxation is a type of recognizable luxation injury represented by a deeper axial displacement of the tooth toward the alveolar bone. Treatment strategies include waiting for the tooth to return to its position, immediate surgical repositioning, and repositioning through dental traction by orthodontic devices. The aim of this case report was to present the management of severe dental trauma and later restoration following IADT. A 20-year-old patient was presented after fainting at home four hours before, resulting in a dento-alveolar trauma. Clinical examinations revealed a traumatic intrusion, in 1.2, 1.1 and 2.1, uncomplicated crown fractures in 1.1 and 2.1 and a complicated crown-root fracture in 2.2. The diagnosis was confirmed with CBCT. Following IADT protocol, the emergency treatment consisted of the surgical repositioning and semi-rigid splinting using orthodontic wire-composite, replacing the buccal bone plate, and postoperative instructions to the patient regarding oral hygiene. After 2 weeks the root canal treated and filled with fiberglass posts in 1.2, 1.1, 2.1 and 2.2. Splint was removed after 4 weeks and the IADT reassessment protocol followed, with revisions at 6-8 weeks, 6 months, a year and annual reviews for 5 years. A year after the treatment, the traumatized teeth were restored with minimally invasive preparations of feldspathic ceramic. Esthetics and function were recorded with a 3-year follow-up period. Key words:Intrusive luxation, dental trauma, crown-root fracture, dento-alveolar trauma, permanent tooth, CBCT.

  16. Genotoxicity evaluation of pesticide formulations containing alachlor and atrazine in multiple mouse tissues (blood, kidney, liver, bone marrow, spleen) by comet assay.

    Science.gov (United States)

    Zeljezic, D; Garaj-Vrhovac, V

    2004-01-01

    Every year, in the European countries more than 2 million tons of pesticides are released into the environment. More than 60% of those substances appear to be herbicides. Due to extensive production and application of this chemical their putative detrimental effect on life should be known and minimized. In this study we applied the comet assay on blood and 4 mouse organs (kidney, liver, bone marrow, and spleen) to evaluate possible genome damage caused by two pesticide formulations (Bravo and Gesaprim) containing alachlor and atrazine as active ingredients. Five male CBA mice were assigned to each of 4 treatment groups and control group. Bravo and Gesaprim were injected intraperitoneally once. Two different doses of Bravo were used: 0.031 ml/kg and 0.021 microl/kg, so that doses of alachlor mice received within the pesticide formulation given were 15 mg/kg and 0.01 mg/kg. Also Gesaprim was given at two different doses: 1.08 ml/kg and 0.07 microl/kg so that the doses of atrazine contained within the pesticide formulation given were 540 mg/kg and 3.5 x 10(-2) mg/kg. Mice were sacrificed 24 hours after treatment. Alkaline comet assay on the blood samples, kidney, liver, bone marrow and spleen was performed. Statistically significant (ppesticides DNA of kidney and liver showed largest increase in migration. Also, distribution of tail length values for Bravo and Gesaprim for all mouse tissues examined showed a shift to the right when compared to the controls.

  17. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

    Science.gov (United States)

    Rafelski, Susanne M.; Keller, Lani C.; Alberts, Jonathan B.; Marshall, Wallace F.

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  18. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication.

    Science.gov (United States)

    Rafelski, Susanne M; Keller, Lani C; Alberts, Jonathan B; Marshall, Wallace F

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  19. Trypanosoma vivax, T. congolense "forest type" and T. simiae: prevalence in domestic animals of sleeping sickness foci of Cameroon.

    Science.gov (United States)

    Nimpaye, H; Njiokou, F; Njine, T; Njitchouang, G R; Cuny, G; Herder, S; Asonganyi, T; Simo, G

    2011-05-01

    In order to better understand the epidemiology of Human and Animal trypanosomiasis that occur together in sleeping sickness foci, a study of prevalences of animal parasites (Trypanosoma vivax, T. congolense "forest type", and T. simiae) infections was conducted on domestic animals to complete the previous work carried on T. brucei gambiense prevalence using the same animal sample. 875 domestic animals, including 307 pigs, 264 goats, 267 sheep and 37 dogs were sampled in the sleeping sickness foci of Bipindi, Campo, Doumé and Fontem in Cameroon. The polymerase chain reaction (PCR) based method was used to identify these trypanosome species. A total of 237 (27.08%) domestic animals were infected by at least one trypanosome species. The prevalence of T. vivax, T. congolense "forest type" and T. simiae were 20.91%, 11.42% and 0.34% respectively. The prevalences of 7 vivax and T. congolense "forest type" differed significantly between the animal species and between the foci (p < 0.0001); however, these two trypanosomes were found in all animal species as well as in all the foci subjected to the study. The high prevalences of 7 vivax and T congolense "forest type" in Bipindi and Fontem-Center indicate their intense transmission in these foci.

  20. Bone cutting.

    Science.gov (United States)

    Giraud, J Y; Villemin, S; Darmana, R; Cahuzac, J P; Autefage, A; Morucci, J P

    1991-02-01

    Bone cutting has always been a problem for surgeons because bone is a hard living material, and many osteotomes are still very crude tools. Technical improvement of these surgical tools has first been their motorization. Studies of the bone cutting process have indicated better features for conventional tools. Several non-conventional osteotomes, particularly ultrasonic osteotomes are described. Some studies on the possible use of lasers for bone cutting are also reported. Use of a pressurised water jet is also briefly examined. Despite their advantages, non-conventional tools still require improvement if they are to be used by surgeons.

  1. Multiple Myeloma Overview

    Science.gov (United States)

    ... be worse. The 2 medicines most often used together to treat multiple myeloma are melphalan (a chemotherapy drug) and prednisone (a steroid medicine).If you have multiple myeloma, you should try to stay active. Staying active helps keep the calcium in your bones ...

  2. Temporal bone chondroblastoma totally invisible on MRI.

    Science.gov (United States)

    Hiraumi, Harukazu; Arakawa, Yoshiki; Yamamoto, Norio; Sakamoto, Tatsunori; Ito, Juichi

    2016-08-01

    We report a case of temporal bone chondroblastoma that was totally invisible on MRI. The patient was a 64-year-old man who presented with several months history of vertigo. The CT scan with bone window setting showed destruction of the temporomandibular joint, the floor of the middle cranial fossa, and the superior semicircular canal. Calcific foci were seen within the tumor. On MR imaging, the tumor, situating mainly medial to the temporomandibular joint, showed no signal on both T1- and T2-weighted images. The tumor was not enhanced with gadolinium. In summary, the tumor was totally signal negative or "invisible" on pre- and postcontrast T1- and T2-weighted images. The tumor was resected through transpetrosal - transzygomatic approach.

  3. Cytoplasmic CUG RNA foci are insufficient to elicit key DM1 features.

    Directory of Open Access Journals (Sweden)

    Warunee Dansithong

    Full Text Available The genetic basis of myotonic dystrophy type I (DM1 is the expansion of a CTG tract located in the 3' untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG(400 repeat tract was positioned 3' of the termination codon and 5' of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA

  4. γH2AX Foci Form Preferentially in Euchromatin after Ionising-Radiation

    Science.gov (United States)

    Cowell, Ian G.; Sunter, Nicola J.; Singh, Prim B.; Austin, Caroline A.; Durkacz, Barbara W.; Tilby, Michael J.

    2007-01-01

    Background The histone variant histone H2A.X comprises up to 25% of the H2A complement in mammalian cells. It is rapidly phosphorylated following exposure of cells to double-strand break (DSB) inducing agents such as ionising radiation. Within minutes of DSB generation, H2AX molecules are phosphorylated in large chromatin domains flanking DNA double-strand breaks (DSBs); these domains can be observed by immunofluorescence microscopy and are termed γH2AX foci. H2AX phosphorylation is believed to have a role mounting an efficient cellular response to DNA damage. Theoretical considerations suggest an essentially random chromosomal distribution of X-ray induced DSBs, and experimental evidence does not consistently indicate otherwise. However, we observed an apparently uneven distribution of γH2AX foci following X-irradiation with regions of the nucleus devoid of foci. Methodology/Principle Findings Using immunofluorescence microscopy, we show that focal phosphorylation of histone H2AX occurs preferentially in euchromatic regions of the genome following X-irradiation. H2AX phosphorylation has also been demonstrated previously to occur at stalled replication forks induced by UV radiation or exposure to agents such as hydroxyurea. In this study, treatment of S-phase cells with hydroxyurea lead to efficient H2AX phosphorylation in both euchromatin and heterochromatin at times when these chromatin compartments were undergoing replication. This suggests a block to H2AX phosphorylation in heterochromatin that is at least partially relieved by ongoing DNA replication. Conclusions/Significance We discus a number of possible mechanisms that could account for the observed pattern of H2AX phosphorylation. Since γH2AX is regarded as forming a platform for the recruitment or retention of other DNA repair and signaling molecules, these findings imply that the processing of DSBs in heterochromatin differs from that in euchromatic regions. The differential responses of

  5. ON STRUCTURED AND DIFFUSE SEISMICITY, STIFFNESS OF EARTHQUAKE FOCI, AND NONLINEARITY OF MAGNITUDE RECURRENCE GRAPHS

    Directory of Open Access Journals (Sweden)

    Evgeny G. Bugaev

    2015-09-01

    Full Text Available Geological, geophysical and seismogeological studies are now conducted in a more detail and thus provide for determining seismic sources with higher accuracy, from the first meters to first dozens of meters [Waldhauser, Schaff, 2008]. It is now possible to consider uncertainty ellipses of earthquake hypocenters, that are recorded in the updated Earthquake Catalogue, as surfaces of earthquake focus generators. In our article, it is accepted that a maximum horizontal size of an uncertainty ellipse corresponds to an area of a focus generator, and seismic events are thus classified into two groups, earthquakes with nonstiff and stiff foci. Criteria of such a classification are two limits of elastic strain and brittle strain in case of uniaxial (3⋅10–5 or omnidirectional (10–6 compression. The criteria are established from results of analyses of parameters of seismic dislocations and earthquake foci with regard to studies of surface parameters and deformation parameters of fault zones. It is recommendable that the uniaxial compression criterion shall be applied to zones of interaction between tectonic plates, and the unilateral compression criterion shall be applied to low active (interplate areas. Sample cases demonstrate the use of data sets on nonstiff and stiff foci for separate evaluation of magnitude reoccurrence curves, analyses of structured and dissipated seismicity, review of the physical nature of nonlinearity of recurrence curves and conditions of preparation of strong earthquakes. Changes of parameters of the recurrence curves with changes of data collection square areas are considered. Reviewed are changes of parameters of the recurrence curves during preparation for the Japan major earthquake of 11 March 2011 prior to and after the major shock. It is emphasized that it is important to conduct even more detailed geological and geophysical studies and to improve precision and sensitivity of local seismological monitoring networks

  6. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    Full Text Available BACKGROUND: Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. METHODOLOGY/PRINCIPAL FINDINGS: We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. CONCLUSION/SIGNIFICANCE: Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after

  7. Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence.

    Science.gov (United States)

    Willitzki, Annika; Lorenz, Sebastian; Hiemann, Rico; Guttek, Karina; Goihl, Alexander; Hartig, Roland; Conrad, Karsten; Feist, Eugen; Sack, Ulrich; Schierack, Peter; Heiserich, Lisa; Eberle, Caroline; Peters, Vanessa; Roggenbuck, Dirk; Reinhold, Dirk

    2013-11-01

    Analysis of phosphorylated histone protein H2AX (γH2AX) foci is currently the most sensitive method to detect DNA double-strand breaks (DSB). This protein modification has the potential to become an individual biomarker of cellular stress, especially in the diagnosis and monitoring of neoplastic diseases. To make γH2AX foci analysis available as a routine screening method, different software approaches for automated immunofluorescence pattern evaluation have recently been developed. In this study, we used novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescence images of γH2AX foci and compared the results with visual assessments. Dose- and time-dependent γH2AX foci formation was investigated in human peripheral blood mononuclear cells (PBMCs) treated with the chemotherapeutic drug etoposide (ETP). Moreover, the AKLIDES system was used to analyze the impact of different immunomodulatory reagents on γH2AX foci formation in PBMCs. Apart from γH2AX foci counting the use of novel pattern recognition algorithms allowed the measurement of their fluorescence intensity and size, as well as the analysis of overlapping γH2AX foci. The comparison of automated and manual foci quantification showed overall a good correlation. After ETP exposure, a clear dose-dependent increase of γH2AX foci formation was evident using the AKLIDES as well as Western blot analysis. Kinetic experiments on PBMCs incubated with 5 μM ETP demonstrated a peak in γH2AX foci formation after 4 to 8 h, while a removal of ETP resulted in a strong reduction of γH2AX foci after 1 to 4 h. In summary, this study demonstrated that the AKLIDES system can be used as an efficient automatic screening tool for γH2AX foci analysis by providing new evaluation features and facilitating the identification of drugs which induce or modulate DNA damage.

  8. [Multiple organ relapse in primary de novo CD5+ diffuse large B cell lymphoma of the bone after a complete response].

    Science.gov (United States)

    Nakayama, Shoko; Akioka, Toshikazu; Yokote, Taiji; Hara, Satoshi; Oka, Satoko; Yamane, Kazushi; Yamano, Takeshi; Tsuji, Motomu; Hanafusa, Toshiaki

    2004-02-01

    A 57-year-old woman was admitted with swelling of the femur. MRI showed that an intramedullary lesion had expanded from the trunk to the distal portion where it had formed an extramedullary tumor mass. An open biopsy showed diffuse proliferation of abnormal lymphoid cells. Immunohistochemical staining and flow cytometry demonstrated LCA+, CD3-, CD23-, CD79a+, CD5+, IgM+, IgD- and kappa + and cyclin D1-. FISH analysis did not detect t(11;14)(q13;q32). The final diagnosis was de novo CD5+ diffuse large B-cell lymphoma (DLBL) of the bone at clinical stage IEA. The patient suffered a pathological fracture in the femur after two courses of CHOP. The therapy was changed to ESHAP and irradiation. The result was assessed as a complete remission (CR). One month later, the patient presented with epigastric pain. MRI showed the tumor at the spleen and kidney and hydronephrosis due to pelvic lymphadenopathy, but did not show a tumor in the femur. An open biopsy of the pelvic lymph node showed relapse. The tumor and hydronephrosis disappeared and necrosis in the kidney was observed on MRI after ESHAP. De novo CD5+ DLBL appears to constitute a unique subset of DLBL with an aggressive clinical course and requires established therapeutic strategies.

  9. Cancer Cell Colonisation in the Bone Microenvironment

    Science.gov (United States)

    Kan, Casina; Vargas, Geoffrey; Le Pape, François; Clézardin, Philippe

    2016-01-01

    Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow. PMID:27782035

  10. Cancer Cell Colonisation in the Bone Microenvironment

    Directory of Open Access Journals (Sweden)

    Casina Kan

    2016-10-01

    Full Text Available Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow.

  11. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

    Directory of Open Access Journals (Sweden)

    Orner Gayle A

    2006-02-01

    Full Text Available Abstract Chlorophyllin (CHL is a promising chemopreventive agent believed to block cancer primarily by inhibiting carcinogen uptake through the formation of molecular complexes with the carcinogens. However, recent studies suggest that CHL may have additional biological effects particularly when given after the period of carcinogen treatment. This study examines the post-initiation effects of CHL towards aflatoxin B1 (AFB1-induced preneoplastic foci of the liver and colon. The single concentration of CHL tested in this study (0.1% in the drinking water had no significant effects on AFB1-induced foci of the liver and colons of rats.

  12. Demonstration lessons in mathematics education: teachers' observation foci and intended changes in practice

    Science.gov (United States)

    Clarke, Doug; Roche, Anne; Wilkie, Karina; Wright, Vince; Brown, Jill; Downton, Ann; Horne, Marj; Knight, Rose; McDonough, Andrea; Sexton, Matthew; Worrall, Chris

    2013-06-01

    As part of a teacher professional learning project in mathematics education, university mathematics educators taught demonstration lessons in project primary schools. These lessons were part of a "pre-brief, teaching, and debrief" process, in which up to eight teachers observed each lesson. Using brief questionnaires completed in advance of the lesson, during the lesson, following the debrief, and several weeks later, data were collected on teachers' intended and actual observation foci and any anticipated changes in their beliefs and practices arising from the experience. There were several common themes in teachers' intended observations, including a focus on questioning, catering for individual differences, and building student engagement. As evident in other research, teachers' intended and actual observations gave greater attention to teacher actions and decision making than to student learning and thinking. In this paper, we situate demonstration lessons within teacher professional learning models, describe the features of our model, summarise teacher data, and discuss issues arising from our work.

  13. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Tang, Jonathan; Georgescu, Walter; Costes, Sylvain V.

    2013-10-01

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  14. Canine Uterine Leiomyoma with Epithelial Tissue Foci, Adenomyosis, and Cystic Endometrial Hyperplasia

    Directory of Open Access Journals (Sweden)

    George S. Karagiannis

    2011-01-01

    Full Text Available An 11-year-old Labrador Retriever bitch with a history of intermittent, sanguineous vaginal discharge of a six-month duration was presented. During exploratory laparotomy, two well-delineated, intramural masses were identified bilaterally in the uterine horns. Histopathologic examination of the mass on the left horn showed that it was a typical leiomyoma. However, the second mass appeared with an unusual coexistence of histological lesions, involving epithelial tissue foci, mild focal adenomyosis, and cystic endometrial hyperplasia. Interestingly, such combination was never encountered before in dogs. Although uterine leiomyoma is quite usual in the reproductive system of female dogs, this case resembled relevant cases of human uterine adenomyomas in morphology, and thus it was offered a similar tentative diagnosis.

  15. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Georgescu, Walter; Tang, Jonathan; Costes, Sylvain V.

    2013-09-03

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  16. Aberrant crypt foci in the colo-rectal mucosa as reliable markers of tumor development

    DEFF Research Database (Denmark)

    Thorup, Inger

    The aim of the present thesis has been to evaluate a recently developed short term in vivo model, the aberrant crypt foci bioassay (ACF), for its ability to predict the development of colo-rectal tumors. Based on the knowledge obtained during the last decade, it can be stated that no simple...... connection exists between occurrence of ACF (neither qualitatively nor quantita- tively) and later development of tumors. However, the literature has shown that part of the ACF show morphologic and genetic features characteristic for the tumorigenic process and a recent investigation indicate that all ACF...... belong to the same unity with basically the same chances for gradual progressing into tumors. It may be speculated that the progression depends on promo- tional conditions in the environment....

  17. Multifocal bone and bone marrow lesions in children - MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Raissaki, Maria; Demetriou, Stelios; Spanakis, Konstantinos; Skiadas, Christos; Karantanas, Apostolos H. [University of Crete, Faculty of Medicine, Department of Radiology, University Hospital of Heraklion, Heraklion, Crete (Greece); Katzilakis, Nikolaos; Stiakaki, Eftichia [University of Crete, Faculty of Medicine, Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Crete (Greece); Velivassakis, Emmanouil G. [University Hospital of Heraklion, Orthopedic Clinic, Heraklion, Crete (Greece)

    2017-03-15

    Polyostotic bone and bone marrow lesions in children may be due to various disorders. Radiographically, lytic lesions may become apparent after loss of more than 50% of the bone mineral content. Scintigraphy requires osteoblastic activity and is not specific. MRI may significantly contribute to the correct diagnosis and management. Accurate interpretation of MRI examinations requires understanding of the normal conversion pattern of bone marrow in childhood and of the appearances of red marrow rests and hyperplasia. Differential diagnosis is wide: Malignancies include metastases, multifocal primary sarcomas and hematological diseases. Benign entities include benign tumors and tumor-like lesions, histiocytosis, infectious and inflammatory diseases, multiple stress fractures/reactions and bone infarcts/ischemia. (orig.)

  18. Multiple myeloma.

    Science.gov (United States)

    Anderson, Kenneth C; Shaughnessy, John D; Barlogie, Bart; Harousseau, Jean-Luc; Roodman, G David

    2002-01-01

    This update provides new insights into the biology, diagnosis, prognosis, and treatment of multiple myeloma (MM) and its complications. In Section I, Drs. John Shaughnessy, Jr., and Bart Barlogie first correlate global gene microarray expression profiling of patient MM samples with normal plasma cells to provide the basis for a developmental stage-based classification of MM. The powerful clinical utility of these analyses is illustrated in delineating mechanism of drug action, identifying novel therapeutic targets, and providing a molecular analysis not only of the tumor cell, but also of the tumor microenvironment, in MM. In Section II, Dr. Jean-Luc Harousseau reviews the rationale and current results of high dose therapy and autologous stem cell transplantation in MM, including optimal patient selection, prognostic factors, conditioning regimens, sources of stem cells, use of tandem transplantation, and maintenance therapy. He then provides an update on the results of allotransplantation approaches in MM, focusing on proposed methods to reduce toxicity and exploit the graft-versus-MM alloimmune effect by transplantation earlier in the disease course, T cell depletion, and nonmyeloablative transplantation. In Section III, Dr. G. David Roodman provides recent insights into the mechanisms of osteoclast activation, interactions between bone and MM cells, adhesive interactions in MM bone disease, and osteoblast suppression. These recent advances not only provide insights into pathogenesis of MM bone disease, but also form the framework for novel therapeutics. In Section IV, Dr. Kenneth Anderson provides an up-to-date discussion of the role of the bone marrow microenvironment in promoting growth, survival, drug resistance, and migration of MM cells and the signaling cascades mediating these sequelae. These studies provide the framework for evaluation of novel therapeutics targeting the MM cell-host interaction in vivo in animal models and in derived clinical trials.

  19. The Adequacy of the Q Methodology for Clinical Validation of Nursing Diagnoses Related to Subjective Foci.

    Science.gov (United States)

    Miguel, Susana; Caldeira, Sílvia; Vieira, Margarida

    2016-11-17

    This article describes the adequacy of the Q methodology as a new option for the validation of nursing diagnoses related to subjective foci. Discussion paper about the characteristics of the Q methodology. This method has been used in nursing research particularly related to subjective concepts and includes both a quantitative and qualitative dimension. The Q methodology seems to be an adequate and innovative method for the clinical validation of nursing diagnoses. The validation of nursing diagnoses related to subjective foci using the Q methodology could improve the level of evidence and provide nurses with clinical indicators for clinical reasoning and for the planning of effective interventions. Descrever a adequação da metodologia Q como uma nova opção para a validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos. MÉTODOS: Artigo de discussão sobre as características da metodologia Q. Este método tem sido utilizado na pesquisa em enfermagem relacionada com conceitos subjetivos e inclui em simultâneo uma vertente qualitativa e quantitativa. CONCLUSÕES: A metodologia Q parece ser uma opção metodológica adequada para a validação clínica de diagnósticos de enfermagem. IMPLICAÇÕES PARA A PRÁTICA: A utilização da metodologia Q na validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos pode melhorar o nível e evidência e facilitar o raciocínio clínico dos enfermeiros, ao providenciar indicadores clínicos também necessários ao desenvolvimento de intervenções efetivas. © 2016 NANDA International, Inc.

  20. Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo

    Institute of Scientific and Technical Information of China (English)

    Ying-Fang Fan; Zong-Hai Huang

    2002-01-01

    AIM: To study the effect of angiogenesis inhibitor TNP-470on peritoneal dissemination of colon cancer in nude mice,METHODS: The MTT assay was used to evaluate theinhibitory effect of TNP-470 on human colon cancer cell lineLovo. Lovo cells were injected into the peritoneal cavity ofBABL/C nu/nu mice and the models of peritonealdissemination were developed. Thirty nude mice wererandomly divided into control and TNP-470-treated group.In TNP-470-treated group, TNP-470 was injectedsubcutaneously every other day from day 1 until sacrifice ordeath (30 mg.kg-1). The control group received a shaminjection of the same volume saline solutionRESULTS: In vltro, TNP-470 inhibited the growth of Lovocells, with its IC50 at 2.14x102μg.L-1 In vivo, TNP-470demonstrated growth inhibition of tumors. Mice body weightand abdominal circumferences were significantly differentbetween TNP-470-treated group (24.5±3.2 g, 7.0±1.1 cm)and control group (29.5±2.1 g, 10.3±1.5 cm), P=0.005 andP=0.001. The number of disseminated foci was significantlydifferent between the control group (92.1±20.6) and theTNP-470-treated group (40.3±12.3), P<0.001. The maximalsize of foci was significantly smaller in TNP-470-treated group(3.3±0.7 mm) than that of control (7.3±2.3 mm), P=0.004.Mean survival time was significantly longer in TNP-470-treated group(98.00±12.06 d) than that in control group(41.86±9.51 d), P<0.001.CONCLUSION: Angiogenesis inhibitor TNP-470 might beeffective in treating peritoneal dissemination of colon cancerand improve the survival rate of nude mice.

  1. Oncologic progression of bone plasmacytomas to multiple myeloma Evolução oncológica dos plasmocitomas ósseos para mieloma múltiplo

    Directory of Open Access Journals (Sweden)

    Fernanda Bertanha

    2006-04-01

    Full Text Available PURPOSE: To evaluate the clinical aspects, diagnoses, prognostic factors, and percent progression of plasmacytoma to multiple myeloma. MATERIALS AND METHODS: 103 medical records of patients suspected of plasmacytoma were surveyed covering the period between 1950 and 1998, and 30 were selected for analysis. Patients were classified into 2 groups: patients who did (n = 17 and did not (n = 13 progress to multiple myeloma. Comparative statistics regarding a variety of clincial aspects were developed. RESULTS: Patients who progressed to multiple myeloma were younger than those who did not (52.3 ± 2.6 vs 62.6 ± 3.4 years; mean ± SEM; P = 0.02. There were no significant differences in gender between groups. A higher incidence of multiple recurrence was observed in patients who progressed to multiple myeloma (75%, P = 0.049. Both groups showed a prevalence of vertebral column injuries. No significant differences were found between groups regarding the disease period (from the onset of symptoms until diagnosis (P = 0.20 and survival (P = 0.34. The average time to progression from plasmacytoma to myeloma was 41 ± 39 months (mean ± SD, and the progression rate was 57%. CONCLUSION: Patients who progressed to multiple myeloma were younger than those who did not. No significant differences were found between groups regarding sex, time from symptom onset to diagnosis, and survival time. In both groups, the most affected anatomic location was the vertebral column, and most affected sex was male. The average time to progression to multiple myeloma was 41 months. It was not possible to determine the factors that influenced the survival of patients with plasmacytoma or for those who progressed to multiple myeloma.OBJETIVO: Avaliar os aspectos clínicos, diagnósticos, fatores de prognóstico e porcentagem de evolução dos casos de plasmocitoma para mieloma múltiplo. MATERIAS E MÉTODOS: Foram levantados 103 prontuários do Hospital das Clínicas da FMUSP

  2. Gaucher disease and bone manifestations.

    Science.gov (United States)

    Marcucci, Gemma; Zimran, Ari; Bembi, Bruno; Kanis, John; Reginster, Jean-Yves; Rizzoli, Renè; Cooper, Cyrus; Brandi, Maria Luisa

    2014-12-01

    Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.

  3. Novel Adipokines and Bone Metabolism

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-01-01

    Full Text Available Osteoporosis is a serious social issue nowadays. Both the high morbidity and its common complication osteoporotic fracture load a heavy burden on the whole society. The adipose tissue is the biggest endocrinology organ that has a different function on the bone. The adipocytes are differentiated from the same cell lineage with osteoblast, and they can secrete multiple adipokines with various functions on bone remolding. Recently, several novel adipokines have been identified and investigated thoroughly. In this paper, we would like to highlight the complicated relation between the bone metabolism and the novel adipokines, and it may provide us with a new target for prediction and treatment of osteoporosis.

  4. Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection

    Energy Technology Data Exchange (ETDEWEB)

    Fujisawa, Hiroshi [School of Engineering, The University of Tokyo, Tokyo 113-8656 (Japan); Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Fujimori, Akira [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Uesaka, Mitsuru [School of Engineering, The University of Tokyo, Tokyo 113-8656 (Japan); Yajima, Hirohiko, E-mail: hyajima@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2015-01-15

    Highlights: • CtIP becomes hyperphosphorylated and forms foci following cell irradiation. • CtIP accumulates in foci subsequent to the peak of hyperphosphorylation. • CtIP is maintained in a hypophosphorylated state at later times. • CtIP is continuously recruited to DNA double strand breaks downstream of resection. • CtIP presumably have a distinct role following the initiation of resection. - Abstract: Homologous recombination (HR) is a major repair pathway for DNA double strand breaks (DSBs), and end resection, which generates a 3′-single strand DNA tail at the DSB, is an early step in the process. Resection is initiated by the Mre11 nuclease together with CtIP. Here, we describe novel characteristics of CtIP at DSBs. At early times following exposure of human cells to ionizing radiation, CtIP localized to the DSB, became hyperphosphorylated and formed foci in an ATM-dependent manner. At later times, when the initiation of resection had occurred, CtIP foci persist but CtIP is maintained in a hypophosphorylated state, which is dependent on ATM and ATR. Exposure to cycloheximide revealed that CtIP turns over at DSB sites downstream of resection. Our findings provide strong evidence that CtIP is continuously recruited to DSBs downstream of both the initiation and extension step of resection, strongly suggesting that CtIP has functions in addition to promoting the initiation of resection during HR.

  5. AFSC/RACE/EcoFOCI: 2011 Gulf of Alaska Late Larval Survey DY11-02/2DY11

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A total of 70 stations were occupied. The standard FOCI grid and line 8 were samped. At each station we sampled using paired 20 and 60 cm Bongo frames (150 and 500...

  6. Effect of dietary galacto-oligosaccharides on azoxymethane-induced aberrant crypt foci and colorectal cancer in Fischer 344 rats

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Schoterman, H.C.; Bruijntjes, J.P.; Hollanders, V.M.H.; Woutersen, R.A.

    2001-01-01

    The aim of the present study was to investigate the effects of galacto-oligosaccharides (GOS, Elix'or) on the development of aberrant crypt foci (ACF) and colorectal tumours in rats treated with azoxymethane (AOM). Two groups of 102 male Fischer 344 rats were injected twice with AOM to induce colore

  7. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.

    Science.gov (United States)

    Lee, Youn-Bok; Chen, Han-Jou; Peres, João N; Gomez-Deza, Jorge; Attig, Jan; Stalekar, Maja; Troakes, Claire; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline; Adachi, Yoshitsugu; Sardone, Valentina; Miller, Jack W; Smith, Bradley N; Gallo, Jean-Marc; Ule, Jernej; Hirth, Frank; Rogelj, Boris; Houart, Corinne; Shaw, Christopher E

    2013-12-12

    The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

  8. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  9. Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Erk, van M.J.; Doornbos, R.P.; Krul, C.A.M.; Woutersen, R.A.

    2004-01-01

    The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2%

  10. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  11. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  12. Bone graft

    Science.gov (United States)

    ... around the area. The bone graft can be held in place with pins, plates, or screws. Why ... Orthopaedic Surgery, San Francosco, CA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  13. Flowcytometric evaluation of cell cycle regulators (cyclins and cyclin dependent kinase inhibitors expressed on bone marrow cells of patients with chronic myelogenous leukemia and multiple myeloma

    Directory of Open Access Journals (Sweden)

    Selami Koçak Toprak

    2012-03-01

    Full Text Available OBJECTIVE: Etiopathology of malignancy can be demonstrated by the comparison of the quantified changes in the different phases of the cycle about cyclins and cyclin dependent kinase inhibitors (CDKI in healthy and malignant proliferated cells. The aim of this study is to analyze flow cytometric expression of cell cycle regulating elements in the malignant diseases with low and high proliferative signature. METHODS: The levels of cyclin D, E, A, B and CDKI's p16, p21 were studied by flowcytometry in patients with chronic myeloid leukemia (CML (n=16, multiple myeloma (MM (n=13 and control subjects (n=15. RESULTS: The distributions of the cell cycle S phase were 10, 63%, 6, 72% and 3, 59%; for CML, MM and control subjects, respectively. Among all the cyclins expressed during the S phase, cyclin D expression was the lowest, in CML patients. While the distribution of cyclins and CDKI’s was similar between MM and control groups in G2/M phase; cyclins expressions were parallel in all three phases in MM and chronic myeloid leukemia groups. CONCLUSION: CML and MM are diseases presenting with variable degrees of proliferation. The increase of cyclins in cell cycle phases in patient group was not associated with the augmentation of the expression of CDKI’s. This finding may contribute the mechanisms effective in the etiopathogenesis of hematological malignancy.

  14. Subnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: processing at transcription sites or accumulation in SC35 foci.

    Science.gov (United States)

    Pawlicki, Jan M; Steitz, Joan A

    2009-02-01

    MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate expression of their target messenger RNAs. We recently demonstrated that primary miRNA transcripts (pri-miRNAs) retained at transcription sites are processed with enhanced efficiency, suggesting that pri-miRNA processing is coupled to transcription in mammalian cells. We also observed that transiently expressed pri-miRNAs accumulate in nuclear foci with splicing factor SC35 and Microprocessor components, Drosha and DGCR8. Here, we show that pri-miRNAs containing a self-cleaving hepatitis delta ribozyme accumulate in the nucleoplasm after release from their transcription sites, but are not efficiently processed. Pri-miRNAs with ribozyme-generated 3' ends do not localize to SC35-containing foci, whereas cleaved and polyadenylated pri-miRNA transcripts with or without the pre-miRNA hairpin do. Pri-miRNA/SC35 foci contain a number of proteins normally associated with SC35 domains, including ASF/SF2, PABII, and the prolyl isomerase, Pin1. In contrast, RNA polymerase II and PM/Scl-100 do not strongly colocalize with pri-miRNAs in SC35-containing foci. These data argue that pri-miRNA/SC35-containing foci are not major sites of pri-miRNA processing and that pri-miRNA processing is coupled to transcription. We discuss the implications of our findings relative to recent insights into miRNA biogenesis, mRNA metabolism, and the nuclear organization of gene expression.

  15. Low Bone Density

    Science.gov (United States)

    ... Information › Bone Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your ... compared to people with normal bone density. Detecting Low Bone Density A bone density test will determine ...

  16. Bone Material Properties in Osteogenesis Imperfecta.

    Science.gov (United States)

    Bishop, Nick

    2016-04-01

    Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density-the quantity of mineral in relation to the quantity of matrix within a specific bone volume-and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment-largely improved architecture and possibly some macroscale toughening-and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales.

  17. 3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice

    Directory of Open Access Journals (Sweden)

    Tai-yong Yu

    2015-01-01

    Full Text Available 3,3′-Diindolylmethane (DIM, a major acid-condensation product or metabolite of indole-3-carbinol which is found in cruciferous vegetables, has been shown to have anticancer, anti-inflammatory, and multiple immune stimulating effects. However, its function in bone metabolism is poorly understood. This study evaluated the effect of DIM on bone mass in mice under physiological and pathological conditions. Eight-week-old female mice received injections of a vehicle or 0.1 mg/g of DIM, twice a week for four weeks. We found that DIM treatment significantly increased bone mass as assessed by dual-energy X-ray absorptiometry (DEXA and micro-computed tomography (μCT. Further, Bone histomorphometric analyses showed that this treatment significantly reduced bone resorption parameters, but did not increase bone formation parameters. Furthermore, we use ovariectomized (OVX-induced osteoporotic mouse model, and explore function of DIM in skeletal pathological processes. Bone phenotype analyses revealed that the administration of DIM in this study effectively prevented OVX-induced bone loss resulting from increased bone resorption. Our results demonstrated that DIM increased bone mass by suppressing osteoclastic bone resorption in bone metabolism under both physiological and pathological conditions. Accordingly, DIM may be of value in the treatment and the possible prevention of bone diseases characterized by bone loss, such as postmenopausal osteoporosis.

  18. Application of multiple teaching method in practice teaching of bone marrow cell morphology%多元式教学在骨髓细胞形态学实践教学中的应用

    Institute of Scientific and Technical Information of China (English)

    梁丽梅; 黄燕; 韦莹慧

    2013-01-01

    Bone marrow cell morphology is the important part of the course of clinical hema-tology and laboratory and is the difficult and key part in the practice teaching of this course. In order to let students better grasp the basic skills, teachers should flexibly use multiple teaching methods of comparison type, communication type, heuristic type, medical record type and PBL type, which will greatly improve the teaching quality of hematology practice teaching.%骨髓细胞形态学是《临床血液学与检验》课程的重要组成部分,也是这门课程实践教学的重点和难点。为了让学生更好地掌握该课程基本技能,在实践教学过程中灵活穿插运用比较式、沟通式、启发式、病案式、以问题为基础的学习(problem-based learning, PBL)等多元教学,提高了血液学检验实践教学质量。

  19. Bone marrow transplant

    Science.gov (United States)

    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 ...

  20. Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.

    Science.gov (United States)

    Hong, Mee Young; Nulton, Emily; Shelechi, Mahshid; Hernández, Lisa M; Nemoseck, Tricia

    2013-01-01

    Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.

  1. Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning

    Science.gov (United States)

    Wolf, Benita; Diop, Fodé; Ferraris, Pauline; Wichit, Sineewanlaya; Busso, Coralie; Missé, Dorothée

    2017-01-01

    Zika virus (ZIKV) causes congenital microcephaly. Although ZIKV can impair cell cycle progression and provoke apoptosis, which probably contributes to disease aetiology through depletion of neural progenitor cells, additional cellular mechanisms may be important. Here, we investigated whether ZIKV infection alters centrosome number and spindle positioning, because such defects are thought to be at the root of inherited primary autosomal recessive microcephaly (MCPH). In addition to HeLa cells, in which centrosome number and spindle positioning can be well monitored, we analysed retinal epithelial cells (RPE-1), as well as brain-derived microglial (CHME-5) and neural progenitor (ReN) cells, using immunofluorescence. We established that ZIKV infection leads to supernumerary foci containing centriolar proteins that in some cases drive multipolar spindle assembly, as well as spindle positioning defects in HeLa, RPE-1 and CHME-5 cells, but not in ReN cells. We uncovered similar phenotypes in HeLa cells upon infection with dengue virus (DENV-2), another flavivirus that does not target brain cells and does not cause microcephaly. We conclude that infection with Flaviviridae can increase centrosome numbers and impair spindle positioning, thus potentially contributing to microcephaly in the case of Zika. PMID:28100662

  2. Contrasting sylvatic foci of Venezuelan equine encephalitis virus in northern South America.

    Science.gov (United States)

    Barrera, Roberto; Ferro, Cristina; Navarro, Juan-Carlos; Freier, Jerome; Liria, Jonathan; Salas, Rosalba; Ahumada, Marta; Vasquez, Clovis; Gonzalez, Marta; Kang, Wenli; Boshell, Jorge; Weaver, Scott C

    2002-09-01

    The ecology of Venezuelan equine encephalitis (VEE) virus transmission was compared at three enzootic foci: two forest sites in the Catatumbo region of western Venezuela that have yielded small numbers of virus isolates since the 1970s, and another focus in the middle Magdalena Valley of Colombia that has consistently yielded many VEE virus isolates. Our results demonstrated dramatic differences in VEE virus isolation rates from sentinel hamsters, as well as differences in mosquito species composition and captured mammals with antibodies to VEE virus, between the Colombian and Venezuelan study sites. The higher isolation rate of enzootic VEE virus in the Colombian site was associated with a more abundant fauna of spiny rats (Proechimys spp.), known reservoir hosts of enzootic VEE virus. Mosquito collections demonstrated that the Colombian forest had a higher mosquito diversity and species evenness than either of the Venezuelan forests. The Colombian focus was especially richer in its Culex (Melanoconion) spp. fauna, a subgenus that includes all proven enzootic vectors for VEE virus. Our results suggest that the greater abundance, diversity, and stability of enzootic vector populations, combined with the greater density of rodent reservoir hosts, explains the higher levels of VEE virus circulation in the Colombian focus compared with the Venezuelan forests.

  3. Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jayadev Raju

    2008-01-01

    The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries.Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans.ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis.For over two decades,since its first discovery,azoxymethane(AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens.Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system.There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up,and extensive research in this field is currently in progress.In chemoprevention studies,AOM-induced rat ACF have been very successful as biomarkers,and have provided several standardized analyses of data.There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome,however,and hence there has been an ambiguity about their role as biomarkers.The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies.The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

  4. Population genetics of Glossina palpalis palpalis from central African sleeping sickness foci

    Directory of Open Access Journals (Sweden)

    Solano Philippe

    2011-07-01

    Full Text Available Abstract Background Glossina palpalis palpalis (Diptera: Glossinidae is widespread in west Africa, and is the main vector of sleeping sickness in Cameroon as well as in the Bas Congo Province of the Democratic Republic of Congo. However, little is known on the structure of its populations. We investigated G. p. palpalis population genetic structure in five sleeping sickness foci (four in Cameroon, one in Democratic Republic of Congo using eight microsatellite DNA markers. Results A strong isolation by distance explains most of the population structure observed in our sampling sites of Cameroon and DRC. The populations here are composed of panmictic subpopulations occupying fairly wide zones with a very strong isolation by distance. Effective population sizes are probably between 20 and 300 individuals and if we assume densities between 120 and 2000 individuals per km2, dispersal distance between reproducing adults and their parents extends between 60 and 300 meters. Conclusions This first investigation of population genetic structure of G. p. palpalis in Central Africa has evidenced random mating subpopulations over fairly large areas and is thus at variance with that found in West African populations of G. p. palpalis. This study brings new information on the isolation by distance at a macrogeographic scale which in turn brings useful information on how to organise regional tsetse control. Future investigations should be directed at temporal sampling to have more accurate measures of demographic parameters in order to help vector control decision.

  5. Motivational foci and asthma medication tactics directed towards a functional day

    Directory of Open Access Journals (Sweden)

    Lötvall Jan

    2011-10-01

    Full Text Available Abstract Background There appears to be an obvious gap between a medical and patient adherence perspective. Deviating from a medication prescription could be regarded as fairly irrational, but with respect to patients' goals and/or concerns it could be seen as understandable. Thus, the aim was to elucidate adherence reasoning in relation to asthma medication. Methods This was a qualitative study; data collection and analysis procedures were conducted according to Grounded Theory methodology. Eighteen persons, aged 22 with asthma and regular asthma medication treatment, were interviewed. Results The emerged theoretical model illustrated that adherence to asthma medication was motivated by three foci, all directed towards a desired outcome in terms of a functional day as desired by the patient. A promotive focus was associated with the ambition to achieve a positive asthma outcome by being adherent either to the received prescription or to a self-adjusted dosage. A preventive focus was intended to ensure avoidance of a negative asthma outcome either by sticking to the prescription or by preventively overusing the medication. A permissive focus was associated with unstructured adherence behaviour in which medication intake was primarily triggered by asthma symptoms. Conclusions As all participants had consciously adopted functioning medication tactics that directed them towards the desired goal of a functional day. In an effort to bridge the gap between a patient- and a medical adherence perspective, patients need support in defining their desired functionality and guidance in developing a person-based medication tactic.

  6. Fluorescence-based SMC and OCT endoscope to study aberrant crypt foci in the mouse colon

    Science.gov (United States)

    Keenan, Molly; Leung, Sarah; Rice, Faith; Wall, R. Andrew; Barton, Jennifer K.

    2013-03-01

    The accepted model of colorectal cancer assumes the paradigm that aberrant crypt foci (ACF) are the earliest events in tumorigenesis and develop into adenoma, which further develop into adenocarcinoma. Under this assumption, basic research and drug studies have been performed using ACF as substitute markers for fully developed carcinoma. While studies have shown a correlation between the number of ACF present and the presence of adenoma/adenocarcinoma, a causal relationship has yet to be determined. The mouse has shown to be an excellent model for colorectal cancer; however, the outcomes of such experiments require sacrifice and histologic examination of ex vivo tissue. To better utilize the mouse model to study ACF and adenoma development, an endoscope was constructed for non-destructive in vivo surface visualization, molecular imaging and cross-sectional imaging of the colon. Our system combines surface magnifying chromoendoscopy (SMC) and optical coherence tomography (OCT) to image colon microstructure. Sixteen mice, treated with the carcinogen azoxymethane, were imaged at 2 week intervals, to visualize carcinogenesis events. With this dual-modality system we are able to visualize crypt structure alteration over time as well as adenoma development over time.

  7. Chromoendoscopy with a Standard-Resolution Colonoscope for Evaluation of Rectal Aberrant Crypt Foci.

    Directory of Open Access Journals (Sweden)

    Marek Kowalczyk

    Full Text Available Colorectal cancer (CRC is the second most common cause of death worldwide. According to the theory by Vogelstein, colorectal carcinogenesis involves a series of successive changes in the normal colonic mucosa, starting with excessive proliferation and focal disorders of intestinal crypts, followed by adenoma and its subsequent malignant transformation. The first identifiable changes in CRC carcinogenesis are aberrant crypt foci (ACF. ACF are invisible during routine colonoscopy yet are well identifiable in chromoendoscopy using methylene blue or indigo carmine. High-resolution colonoscopes are used for assessment of ACF. The aim of the present study was to evaluate the usefulness of standard-resolution colonoscopy for identification of rectal ACF. The following parameters were evaluated: duration of chromoendoscopy of a given rectal segment, type of ACF, sensitivity and specificity of endoscopy combined with histopathological evaluation. The mean duration of colonoscopy and chromoendoscopy was 26.8 min. In the study population, typical ACF were found in 73 patients (p = 0.489, hyperplastic ACF in 49 (p = 0.328, and dysplastic ACF in 16 patients (p = 0.107. Mixed ACF were observed in 11 individuals (p = 0.073. The sensitivity of the method was found to be 0.96 whereas its specificity 0.99. Identification of rectal ACF using standard-resolution colonoscopy combined with rectal mucosa staining with 0.25% methylene blue is characterised by high sensitivity and specificity.

  8. Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague

    Science.gov (United States)

    Koshel, E. I.; Aleshin, V. V.; Eroshenko, G. A.; Kutyrev, V. V.

    2014-01-01

    Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina. PMID:24804197

  9. Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

    Science.gov (United States)

    Evani, Shankar J.; Ramasubramanian, Anand K.

    2016-01-01

    Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

  10. Repair of defects and osteosynthesis of long bones in children with osteoclastoma

    Science.gov (United States)

    Ryzhikov, D. V.; Gubina, E. V.; Podorozhnaya, V. T.; Senchenko, E. V.; Sadovoy, M. A.

    2016-08-01

    The paper is aimed at reporting a retrospective analysis covering the period from 2007 to 2015. The study involved 22 patients with benign osteoclastoma (OC), 14 male and 8 female children aged 9 to 19. All patients had monostotic lesions with the following location of pathological foci: humerus—11 patients, femoral bone—7, shin bone— 1, fibular bone—1, and ulnar bone—1. All 22 patients underwent surgery. Surgical treatment included resection of tumor focus within intact tissues (in cases of eccentric foci, bony bridge was preserved in the area of minimum damage, which was treated by electrocoagulation together with the cavity) together with bone grafting and intramedullary reinforcement of the affected bone (which provides stable osteosynthesis, early mobilization, and prevention of functional deficits in most patients). Consolidation was achieved in 100% of the operated patients.

  11. Diagnostic efficacy of bone scintigraphy, magnetic resonance imaging, and positron emission tomography in bone metastases of myxoid liposarcoma.

    Science.gov (United States)

    Conill, Carlos; Setoain, Xavier; Colomo, Luis; Palacín, Antonio; Combalia-Aleu, Andreu; Pomés, Jaime; Marruecos, Jordi; Vargas, Mauricio; Maurel, Joan

    2008-03-01

    Myxoid liposarcomas (MLS) have a tendency to metastasize to unusual sites. We report an unusual case of bone metastases not detected by bone scan and neither by fluorodeoxyglucose positron emission tomography (PET-FDG) and successfully identified with magnetic resonance imaging (MRI) in a patient with metachronic MLS. Histopathological examination of the primary tumor evidenced a tumor with unfavorable prognostic markers, and the biopsy of an iliac bone lesion confirmed the diagnosis of metastatic disease. On histological grounds, the tumor showed features of a more differentiated neoplasm without foci of round cells or necrosis in the latter. MRI allowed the identification of disseminated disease compared to computed tomography (CT) and PET scans. Thus, because of the heterogeneous histological features of MLS and the biological behavior of the disease, a combined approach of FDGPET-CT and MRI, may allow a more accurate staging of soft tissue sarcomas.

  12. Organ printing: the future of bone regeneration?

    Science.gov (United States)

    Fedorovich, Natalja E; Alblas, Jacqueline; Hennink, Wim E; Oner, F Cumhur; Dhert, Wouter J A

    2011-12-01

    In engineered bone grafts, the combined actions of bone-forming cells, matrix and bioactive stimuli determine the eventual performance of the implant. The current notion is that well-built 3D constructs include the biological elements that recapitulate native bone tissue structure to achieve bone formation once implanted. The relatively new technology of organ/tissue printing now enables the accurate 3D organization of the components that are important for bone formation and also addresses issues, such as graft porosity and vascularization. Bone printing is seen as a great promise, because it combines rapid prototyping technology to produce a scaffold of the desired shape and internal structure with incorporation of multiple living cell types that can form the bone tissue once implanted.

  13. [Encounter of cancer cells with bone. Therapy for bone metastasis from lung cancer].

    Science.gov (United States)

    Sugiura, Hideshi

    2011-03-01

    Bone metastasis from lung cancer requires a thorough examination of bones, including axial bones (e.g., spine, pelvis, and proximal femur) . Most patients have multiple bone metastases by the time they are initially diagnosed. In such patients, radiation therapy is often the first choice of treatment. Surgical treatment is indicated for pathological fracture and impending fracture associated with cortical bone invasion in long bone metastasis. Spinal metastasis requires accurate imaging to evaluate the extent of bone metastasis ; surgical treatment is indicated when the spinal cord is compressed. Given reports that bisphosphonates decrease the incidence of pathological fractures, prescribing bisphosphonates at an early stage is likely to be an effective therapeutic strategy for bone metastasis.

  14. Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

    Science.gov (United States)

    Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

    2014-02-01

    The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases.

  15. Metastatic potential of an aneurysmal bone cyst.

    NARCIS (Netherlands)

    Luijtgaarden, A.C.M. van de; Veth, R.P.H.; Slootweg, P.J.; Wijers-Koster, P.M.; Schultze Kool, L.J.; Bovee, J.V.; Graaf, W.T.A. van der

    2009-01-01

    Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple

  16. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram...... the groups were recorded int erms of: (1) growth rate, (2) body weight at days 14, 28 and 130 of age or (3) final body weight. The weight and length of ribs were, however, significantly increased in the lambs given AKG for the first 14 days of neonatal life by 8.2% and 3.2%, respectively (P....01). Furthermore, AKG administration induced significantly higher bone mineral density of the cortical bone by 7.1% (P

  17. Effect of 89 Sr internal-radiation therapy on 80 patients with multiple metastatic bone cancer%89 Sr 内照射治疗骨转移癌的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    何平; 屈敏

    2016-01-01

    Objective This study explored the effect of 89 Sr internal - radiation therapy on patients with multiple metastatic bone cancer. The study also observed the adverse reactions which occur after treatment. The result may provide a reference for future clinical treatment. Meth-ods This study selected 80 patients with multiple metastatic bone cancer as the object who were treated from January 2009 to January 2011. All patients were given radionuclide 89 Sr intravenous internal - radiation therapy. The clinical and analgesic effect were observed. The effect on hemo-gram was also observed. After the treatment,all patients are followed up for two years. Results After 89 Sr internal - radiation therapy,there were 28 cases(35. 0% )with excellent result and 39 cases(48. 8% )with effective result among the 80 cases. The analgesic efficiency of patients with breast cancer,lung cancer,nasopharyngeal carcinoma,prostate cancer,thyroid cancer,colorectal cancer,uterine cancer,gastric cancer,esopha-geal cancer was 96. 3% ,70. 6% ,75. 0% ,100% ,80. 0% ,100% ,0,0 and 83. 8% . After the internal - radiation therapy,there were 27 cases (33. 8% )who have different levels of white cell division. 27 cases(33. 8% )have different levels of platelet division. The white cells and platelet of all patients return to normal after the hemogram treatment. Before and after treatment,3 to 6 months after the review and follow - up of patients with liver and kidney function when checked,the results showed that 80 cases of liver and kidney function were in normal range. In 67 of 80 cases in the first three months after treatment,the conventional bone scintigraphy results showed lesions of 37 cases disappeared,lesions of 30 cases de-creased or have decreased. 10 cases did not show significant changes in the number of lesions. Conclusion The analgesic effects of drugs or ex-ternal radiation therapy are limited for patients with multiple metastatic bone cancer. The 89 Sr intravenous internal - radiation

  18. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.

    2001-01-01

    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  19. The role of DNA damage and repair in decitabine-mediated apoptosis in multiple myeloma.

    Science.gov (United States)

    Maes, Ken; De Smedt, Eva; Lemaire, Miguel; De Raeve, Hendrik; Menu, Eline; Van Valckenborgh, Els; McClue, Steve; Vanderkerken, Karin; De Bruyne, Elke

    2014-05-30

    DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) are under investigation for the treatment of cancer, including the plasma cell malignancy multiple myeloma (MM). Evidence exists that DNA damage and repair contribute to the cytotoxicity mediated by the DNMTi decitabine. Here, we investigated the DNA damage response (DDR) induced by decitabine in MM using 4 human MM cell lines and the murine 5T33MM model. In addition, we explored how the HDACi JNJ-26481585 affects this DDR. Decitabine induced DNA damage (gamma-H2AX foci formation), followed by a G0/G1- or G2/M-phase arrest and caspase-mediated apoptosis. JNJ-26481585 enhanced the anti-MM effect of decitabine both in vitro and in vivo. As JNJ-26481585 did not enhance decitabine-mediated gamma-H2AX foci formation, we investigated the DNA repair response towards decitabine and/or JNJ-26481585. Decitabine augmented RAD51 foci formation (marker for homologous recombination (HR)) and/or 53BP1 foci formation (marker for non-homologous end joining (NHEJ)). Interestingly, JNJ-26481585 negatively affected basal or decitabine-induced RAD51 foci formation. Finally, B02 (RAD51 inhibitor) enhanced decitabine-mediated apoptosis. Together, we report that decitabine-induced DNA damage stimulates HR and/or NHEJ. JNJ-26481585 negatively affects RAD51 foci formation, thereby providing an additional explanation for the combinatory effect between decitabine and JNJ-26481585.

  20. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... needle is gently pushed and twisted into the bone. Once the sample is obtained, the needle is ... sample is sent to a lab for examination. Bone biopsy may also be done under general anesthesia ...

  1. Facts about Broken Bones

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? Broken Bones KidsHealth > For Kids > Broken Bones Print A A ... sticking through the skin . What Happens When a Bone Breaks? It hurts to break a bone! It's ...

  2. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  3. Broken Bones (For Parents)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Broken Bones KidsHealth > For Parents > Broken Bones Print A A ... bone fragments in place. When Will a Broken Bone Heal? Fractures heal at different rates, depending upon ...

  4. Bone biopsy (image)

    Science.gov (United States)

    A bone biopsy is performed by making a small incision into the skin. A biopsy needle retrieves a sample of bone and it ... examination. The most common reasons for bone lesion biopsy are to distinguish between benign and malignant bone ...

  5. [A study on the taxonomy of soil amoebas from Caspian plague foci based on an analysis of ribosomal operon sequences].

    Science.gov (United States)

    Koshel', E I; Anisimova, L V; Novichkova, L A; Vidiaeva, N A; Guseva, N P; Eroshenko, G A; Kutyrev, V V

    2015-01-01

    The results of a study on the taxonomy and quantitative abundance of free-living amoebas in soil samples from the Russian plague foci of the northwestern Caspian steppe, the Caspian sand, and the Volga-Ural steppe are presented. Amoebas of the Willaertia and Hartmanella genera, as well as representatives of myxomycetes, were isolated from samples. From these, amoebas of the Acanthamoeba genus predominated and could be as abundantas 300000 cells per 1 g of soil. Sequencing of the 18S rRNA gene region showed that Acanthamoeba from the Volga-Ural steppe focus belonged to the A. castellanii species. Phylogenetic analysis confirmed that amoebas from two other Caspian foci belonged to the species of Acanthamoeba spp.

  6. PROBLEMS OF GEOLOGICAL INTERPRETATION OF SEISMIC-FOCI SYSTEMS OF THE EARTH’S CRUST (GEOMECHANICS AND TECTONOPHYSICAL ANALYSIS

    Directory of Open Access Journals (Sweden)

    Boris M. Chikov

    2015-09-01

    Full Text Available In our study, an earthquake focus is viewed as a 3D zone of the Earth’s crust, wherein the discharge of mechanical loading is accompanied by recordable destruction and qualitative transformation of the geological medium. The purpose of the present publication is to make an attempt to reveal a direct relationship between seismicity and deformation-metamorphic processes which took place in the Earth’s crust. Traditional and alternative interpretations of geomechanics of seismic-foci situations are discussed. The problems of geodynamics and geostatics of the seismic-foci systems and their concentrations, as well as anthropogenic models and mechanisms of focus medium structuring are reviewed. The relationship between seismicity and mechanisms of «regional shearing» or formation of crustal deformation-metamorphic structures of lineament type is outlined in the example of the Chuya seismic system of earthquakes which occurred in 2003 and afterwards in the Altai region.

  7. Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells.

    Science.gov (United States)

    Osipov, Andreyan N; Pustovalova, Margarita; Grekhova, Anna; Eremin, Petr; Vorobyova, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry Y; Eremin, Ilya

    2015-09-29

    Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

  8. Genotyping and phylogenetic analysis of Yersinia pestis by MLVA: insights into the worldwide expansion of Central Asia plague foci.

    Directory of Open Access Journals (Sweden)

    Yanjun Li

    Full Text Available BACKGROUND: The species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical non-human pathogenic biovar Microtus (alias Pestoides including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar. METHODOLOGY/PRINCIPAL FINDINGS: Multi-locus VNTR analysis (MLVA with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU, Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci. CONCLUSIONS/SIGNIFICANCE: The results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA

  9. Dose-response relationship of {gamma}-H2AX foci induction in human lymphocytes after X-rays exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mandina, Tania [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Roch-Lefevre, Sandrine H.; Voisin, Pascale [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France); Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Garcia, Omar, E-mail: omar@cphr.edu.cu [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Voisin, Philippe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France)

    2011-09-15

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of {gamma}-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and {gamma}-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y{sub (0.5h)} = 11.66D + 0.15 (R{sup 2} = 0.99), Y{sub (5h)} = 2.44D + 0.15 (R{sup 2} = 0.99), Y{sub (8h)} = 1.57D + 0.22 (R{sup 2} = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using {gamma}-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in {gamma}-H2AX foci kinetics after gamma- and X-irradiation in vitro.

  10. Objective scoring of transformed foci in BALB/c 3T3 cell transformation assay by statistical image descriptors

    OpenAIRE

    Urani, Chiara; Corvi, Raffaella; CALLEGARO G.; Stefanini, Federico Mattia

    2013-01-01

    In vitro cell transformation assays (CTAs) have been shown to model important stages of in vivo carcinogenesis and have the potential to predict carcinogenicity in humans. Advantages of CTAs are their ability of revealing both genotoxic and non-genotoxic carcinogens while reducing both experimental costs and the number of animals used. The endpoint of the CTA is foci formation, and requires classification under light microscopy based on morphology. Thus current limitations for the wide ado...

  11. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Wiegant, Wouter W. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Waisfisz, Quinten [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Medhurst, Annette L. [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N. Copernicus University, Bydgoszcz (Poland)]. E-mail: m.z.zdzienicka@lumc.nl

    2006-02-22

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination.

  12. Detection of γH2AX foci in mouse normal brain and brain tumor after boron neutron capture therapy.

    Science.gov (United States)

    Kondo, Natsuko; Michiue, Hiroyuki; Sakurai, Yoshinori; Tanaka, Hiroki; Nakagawa, Yosuke; Watanabe, Tsubasa; Narabayashi, Masaru; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shin-Ichiro; Ono, Koji

    2016-01-01

    In this study, we investigated γH2AX foci as markers of DSBs in normal brain and brain tumor tissue in mouse after BNCT. Boron neutron capture therapy (BNCT) is a particle radiation therapy in combination of thermal neutron irradiation and boron compound that specifically accumulates in the tumor. (10)B captures neutrons and produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of extremely high linear energy transfer (LET) radiation and therefore have marked biological effects. High LET radiation causes severe DNA damage, DNA DSBs. As the high LET radiation induces complex DNA double strand breaks (DSBs), large proportions of DSBs are considered to remain unrepaired in comparison with exposure to sparsely ionizing radiation. We analyzed the number of γH2AX foci by immunohistochemistry 30 min or 24 h after neutron irradiation. In both normal brain and brain tumor, γH2AX foci induced by (10)B(n,α)(7)Li reaction remained 24 h after neutron beam irradiation. In contrast, γH2AX foci produced by γ-ray irradiation at contaminated dose in BNCT disappeared 24 h after irradiation in these tissues. DSBs produced by (10)B(n,α)(7)Li reaction are supposed to be too complex to repair for cells in normal brain and brain tumor tissue within 24 h. These DSBs would be more difficult to repair than those by γ-ray. Excellent anti-tumor effect of BNCT may result from these unrepaired DSBs induced by (10)B(n,α)(7)Li reaction.

  13. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone...

  14. Detecting Foci of Malaria Transmission with School Surveys: A Pilot Study in the Gambia.

    Directory of Open Access Journals (Sweden)

    Ebako N Takem

    Full Text Available In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community.The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses.A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7 [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124 [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001, while the seroprevalence was 7.8% (234/2994 [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997 [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973 [95% CI = 16.5-23.2 for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920.This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous.

  15. The historical distribution of main malaria foci in Spain as related to water bodies.

    Science.gov (United States)

    Sousa, Arturo; García-Barrón, Leoncio; Vetter, Mark; Morales, Julia

    2014-08-06

    The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO) in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS), using the Inverse Distance Weighted (IDW) interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura), the presence of another vector (Anopheles labranchiae) besides A. atroparvus (Levante) or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia). In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.

  16. Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells.

    Science.gov (United States)

    Vaurijoux, Aurelie; Voisin, Pascale; Freneau, Amelie; Barquinero, Joan Francesc; Gruel, Gaetan

    2017-03-01

    Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5Gy had at least one of these persistent IRIF 24h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Spinocerebellar ataxia type 8 larger triplet expansion alters histone modification and induces RNA foci

    Directory of Open Access Journals (Sweden)

    Wu Yih-Ru

    2009-02-01

    Full Text Available Abstract Background Spinocerebellar ataxia type 8 (SCA8 involves the expression of an expanded CTG/CAG combined repeats (CR from opposite strands producing CUG expansion transcripts (ataxin 8 opposite strand, ATXN8OS and a polyglutamine expansion protein (ataxin 8, ATXN8. The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad. Results Using stably induced cell models expressing 0, 23, 88 and 157 CR, we study the role of ATXN8OS transcripts in SCA8 pathogenesis. In the absence of doxycycline, the stable ATXN8OS CR cell lines exhibit low levels of ATXN8OS expression and a repeat length-related increase in staurosporine sensitivity and in the number of annexin positive cells. A repeat length-dependent repression of ATXN8OS expression was also notable. Addition of doxycycline leads to 25~50 times more ATXN8OS RNA expression with a repeat length-dependent increase in fold of ATXN8OS RNA induction. ChIP-PCR assay using anti-dimethyl-histone H3-K9 and anti-acetyl-histone H3-K14 antibodies revealed increased H3-K9 dimethylation and reduced H3-K14 acetylation around the ATXN8OS cDNA gene in 157 CR line. The repeat length-dependent increase in induction fold is probably due to the increased RNA stability as demonstrated by monitoring ATXN8OS RNA decay in cells treated with the transcriptional inhibitor, actinomycin D. In cells stably expressing ATXN8OS, RNA FISH experiments further revealed ribonuclear foci formation in cells carrying expanded 88 and 157 CR. Conclusion The present study demonstrates that the expanded CUG-repeat tracts are toxic to human cells and may affect ATXN8OS RNA expression and stability through epigenetic and post-transcriptional mechanisms.

  18. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  19. Helicobacter hepaticus infection promotes hepatitis and preneoplastic foci in farnesoid X receptor (FXR deficient mice.

    Directory of Open Access Journals (Sweden)

    Alton G Swennes

    Full Text Available Farnesoid X receptor (FXR is a nuclear receptor that regulates bile acid metabolism and transport. Mice lacking expression of FXR (FXR KO have a high incidence of foci of cellular alterations (FCA and liver tumors. Here, we report that Helicobacter hepaticus infection is necessary for the development of increased hepatitis scores and FCA in previously Helicobacter-free FXR KO mice. FXR KO and wild-type (WT mice were sham-treated or orally inoculated with H. hepaticus. At 12 months post-infection, mice were euthanized and liver pathology, gene expression, and the cecal microbiome were analyzed. H. hepaticus induced significant increases hepatitis scores and FCA numbers in FXR KO mice (P<0.01 and P<0.05, respectively. H. hepaticus altered the beta diversity of cecal microbiome in both WT and FXR KO mice compared to uninfected mice (P<0.05. Significant upregulation of β-catenin, Rela, Slc10a1, Tlr2, Nos2, Vdr, and Cyp3a11 was observed in all FXR KO mice compared to controls (P<0.05. Importantly, H. hepaticus and FXR deficiency were necessary to significantly upregulate Cyp2b10 (P<0.01. FXR deficiency was also a potent modulator of the cecal microbiota, as observed by a strong decrease in alpha diversity. A significant decrease in Firmicutes, particularly members of the order Clostridiales, was observed in FXR KO mice (P<0.05 and FDR<5%, ANOVA. While FXR deficiency strongly affects expression of genes related to immunity and bile acid metabolism, as well as the composition of the microbiome; however, its deficiency was not able to produce significant histopathological changes in the absence of H. hepaticus infection.

  20. Fast and Simple Detection of Yersinia pestis Applicable to Field Investigation of Plague Foci

    Science.gov (United States)

    Simon, Stéphanie; Demeure, Christian; Lamourette, Patricia; Filali, Sofia; Plaisance, Marc; Créminon, Christophe; Volland, Hervé; Carniel, Elisabeth

    2013-01-01

    Yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick) for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37°C. The plasminogen activator (PLA), a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20°C and 37°C, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs). PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA) and an immunostrip (PLA-dipstick), usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition). They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples. PMID:23383008

  1. The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies

    Directory of Open Access Journals (Sweden)

    Arturo Sousa

    2014-08-01

    Full Text Available The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS, using the Inverse Distance Weighted (IDW interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura, the presence of another vector (Anopheles labranchiae besides A. atroparvus (Levante or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia. In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.

  2. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  3. Fast and simple detection of Yersinia pestis applicable to field investigation of plague foci.

    Directory of Open Access Journals (Sweden)

    Stéphanie Simon

    Full Text Available Yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37°C. The plasminogen activator (PLA, a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20°C and 37°C, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs. PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA and an immunostrip (PLA-dipstick, usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition. They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples.

  4. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...... of aged bones....

  5. Physical activity and bone mineral density

    Directory of Open Access Journals (Sweden)

    Međedović Bojan

    2015-01-01

    Full Text Available The bones play an important structural role in the organism. They provide mobility, support, and protect the body, and the place where the storage essential minerals. Healthy bones have a crucial impact on the overall health of a person, and activities that promote health and preventive influence on the formation of bone disease are crucial in maintaining a strong and healthy skeletal system. Physical inactivity affects the decrease in function of bone, and the most common disease of bone osteoporosis. Osteoporosis is a systemic skeletal disorder that results in low bone density and micro-architectural deterioration of bone tissue, that results in less bone density, and may lead to fracture. Physical activity is essential for bone health and prevention of osteoporosis. Based on available information, the best effect to maintain and stimulate the formation of bone mineral density is a combination of dynamic exercises with resistance training that engage multiple joints, large muscle groups, and have influence on the spine and hips. The results suggest that exercises with axial loading, such as running, jumping, and power exercise, promote the positive gains in bone mineral density. Therefore, training should focus on the adaptation of specific parts of the body that is most susceptible to injury, and should be sufficiently intense that exceeds the normal loads.

  6. Multiple factor analysis of lumbar spine bone mass and densities in adolescents with early ankylosing spondylitis%青少年强直性脊柱炎早期腰椎骨密度变化多因素分析

    Institute of Scientific and Technical Information of China (English)

    马兴; 胡蕴玉; 马平; 王全平; 李晓娟; 吕荣; 王军; 徐新智; 吴小明

    2003-01-01

    目的研究青少年强直性脊柱炎(ankylosing spondylitis,AS)早期年龄、身高、体质量、体质量指数(BMI)与L1-4骨矿含量(L1-4BMC)、L1-4面积骨密度(L1-4BMD)、L1-4体积表观骨密度(L1-4BMAD)之间的相关性,旨在初步探讨青少年AS早期骨量、骨密度研究的相关因素和评价指标.方法选择男性青少年强直性脊柱炎早期病例31例,获得年龄、身高、体质量、BMI,应用双能X线骨密度仪(DEXA)检测L1-4BMC,L1-4BMD,并计算L1-4BMAD;采用相关和回归分析研究多因素相关性.结果相关和回归分析表明,身高(P=0.000)和BMI(P=0.009)因素进入L1-4BMC回归方程(R=0.759,Radj2=0.545,P=0 000<0.01),其中身高是L1-4BMC回归方程的关键因素(R=0 676,Radj2=0.439,P=0.000).另外,年龄、身高、体质量和BMI 4因素中只有体质量因素被纳入L1-4BMD回归方程(R=0.657,Radj2=0.412,P=0.000)和L1-4BMAD回归方程(R=0.551,Radj2=0.280,P=0.001).身高和BMI与L1-4BMC显著正相关,体质量则与L1-4BMD和L1-4 BMAD呈显著正相关.结论身高和体质量因素即成为青少年AS早期骨矿含量和骨密度的重要相关因素.%Aim To investigate the possible roles of age, bodyheight, mass and body mass index(BMI) in Lumbar1-4 bone mineralcontent (L1-4BMC), L1-4 areal bone mineral density(L1-44BMD) and L1-4volumetric bone mineral apparent density(L1-4BMAD) of Chinese adoles-cents with early ankylosing spondylitis (AS). Methods Thirty-one maleChinese adolescent outpatients with early AS were included. Age (y),total body mass (kg), height(cn) and body mass index (BMI, kg/m2)of subjects were obtained. L1-44BMC(g) and L1-4 BMD(g/cm2) were e-valuated by using DEXA, and L1-4 BMAD(L1-44BMC/Area3/2, g/cm3)was subsequently calculated. Correlation and multiple regression analyseswere performed. Results Multiple regression revealed that height ( P =0.000) and BMI(P=0.009) were significantly positively related toL1-44BMC (R=0.759, Radj2=0.545, P=0.000 <0.01), and heightplayed

  7. Age dependent T2 changes of bone marrow in pediatric wrist MRI

    Energy Technology Data Exchange (ETDEWEB)

    Shabshin, Nogah [Chaim Sheba Medical Center, Department of Diagnostic Imaging, Tel-HaShomer (Israel); Schweitzer, Mark E. [The Ottawa Hospital, The University of Ottawa, Department of Diagnostic Imaging, Ottawa (Canada)

    2009-12-15

    Hyperintensity of the bone marrow on fluid-sensitive sequences can be seen on magnetic resonance imaging (MRI) during childhood, even in the absence of bone pathology. They can be related to hematopoietic marrow, normal and abnormal bone remodeling. We sought to investigate whether hyper intensity of the bone marrow on MRI of the wrist is age-dependent and to evaluate if this signal follows a consistent age-related pattern. Thirty-one wrist 1.5 T MR images of children (7-18 years) without suspected bone pathology were evaluated for foci of hyperintense bone marrow seen on fluid-sensitive coronal sequences using a scale of 1-3. Correlation of frequency, location and intensity of these foci with age was obtained. Results were analyzed for distribution in single bones and in the following regions: distal forearm, first/second carpal rows, and metacarpal bases. A total of 448 bones were evaluated. Eighty-eight out of 448 (21 out of 31 wrists) showed hyperintense bone marrow seen on fluid-sensitive sequences. The distribution was: radius in 19, ulna in 19, first metacarpal base in 11, scaphoid in 9, lunate in 6, pisiform in 6, and fifth metacarpal base in 1. The involvement of the first and second carpal rows and the metacarpal bases was almost similar (13, 12, and 12 respectively). In the distal forearm, the intensity was similar to or higher than that in the wrist (2.2 vs. 2.0). Frequency decreased with age (100% at 7-9 and 25% at 16-18 years). Foci of hyperintense bone marrow seen on fluid-sensitive sequences can be seen on MRI of the wrist during childhood even without apparent symptoms. It shows a consistent pattern with maturation: frequency and intensity decrease and there is distal-to-proximal resolution. This may be a normal finding that may represent normal bone remodeling or decreasing hematopoietic marrow and should not be confused with pathological bone marrow edema. (orig.)

  8. Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone

    Energy Technology Data Exchange (ETDEWEB)

    Nieuwenhuyse, J.P. van [Department of Radiology and Medical Imaging, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Clapuyt, P. [Department of Radiology and Medical Imaging, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Malghem, J. [Department of Radiology and Medical Imaging, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Everarts, P. [Department of Radiology and Medical Imaging, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Melin, J. [Department of Nuclear Medicine, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Pauwels, S. [Department of Nuclear Medicine, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Brichard, B. [Department of Pediatric Hematology, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Ninane, J. [Department of Pediatric Hematology, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Vermylen, C. [Department of Pediatric Hematology, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium); Cornu, G. [Department of Pediatric Hematology, Cliniques Universitaires St-Luc, University of Louvain Medical School, Brussels (Belgium)

    1996-10-01

    Background. The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. Objective. To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. Materials and methods. Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). Results. Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/RBS+ abnormalities (n = 10) were most frequently insignificant. Conclusion. In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed. (orig.). With 2 figs., 4 tabs.

  9. A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal growth factor receptor signaling in aberrant crypt foci of the colorectum.

    Science.gov (United States)

    Gillen, Daniel L; Meyskens, Frank L; Morgan, Timothy R; Zell, Jason A; Carroll, Robert; Benya, Richard; Chen, Wen-Pin; Mo, Allen; Tucker, Chris; Bhattacharya, Asmita; Huang, Zhiliang; Arcilla, Myra; Wong, Vanessa; Chung, Jinah; Gonzalez, Rachel; Rodriguez, Luz Maria; Szabo, Eva; Rosenberg, Daniel W; Lipkin, Steven M

    2015-03-01

    Colorectal cancer progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal growth factor receptor (EGFR) inhibitors are efficacious in advanced tumors including colorectal cancer. There is significant evidence that EGFR also plays important roles in colorectal cancer initiation, and that EGFR inhibitors block tumorigenesis. We performed a double-blind randomized clinical trial to test whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to colorectal cancer, and normal rectal tissue. A total of 45 patients were randomized to one of three erlotinib doses (25, 50, and 100 mg) with randomization stratified by nonsteroidal anti-inflammatory drug (NSAID) use. There were no unanticipated adverse events with erlotinib therapy. Erlotinib was detected in both normal rectal mucosa and ACFs. Colorectal ACF phosphorylated ERK (pERK), phosphorylated EGFR (pEGFR), and total EGFR signaling changes from baseline were modest and there was no dose response. Overall, this trial did not meet is primary efficacy endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely insufficient to merit further studies without additional prescreening stratification or potentially longer duration of use.

  10. Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Lokesh Kumar Booupathy

    2016-01-01

    Full Text Available Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF. Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.

  11. Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer

    Directory of Open Access Journals (Sweden)

    W. Lunz

    2008-11-01

    Full Text Available We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old were given 4 subcutaneous injections (40 mg/kg body weight each of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH 6.5, at 3-day intervals and divided into three exercise groups that swam with 0% body weight (EG1, N = 11, 2% body weight (EG2, N = 11, and 4% body weight of load (EG3, N = 10, 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10. At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 ± 2.99 vs 36.40 ± 1.53 crypts; P < 0.05. Tumor incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2: 90%; EG3: 80%. Swimming training did not affect either tumor multiplicity (CG: 2.30 ± 0.58; EG1: 2.09 ± 0.44; EG2: 1.27 ± 0.19; EG3: 1.50 ± 0.48 tumors or size (CG: 1.78 ± 0.24; EG1: 1.81 ± 0.14; EG2: 1.55 ± 0.21; EG3: 2.17 ± 0.22 cm³. Intra-abdominal fat was not significantly different among groups (CG: 10.54 ± 2.73; EG1: 6.12 ± 1.15; EG2: 7.85 ± 1.24; EG3: 5.11 ± 0.74 g. Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.

  12. Bone phenotypes of P2 receptor knockout mice

    DEFF Research Database (Denmark)

    Orriss, Isabel; Syberg, Susanne; Wang, Ning

    2011-01-01

    been observed in an impressive number of these mice: distinct abnormalities in P2X7-/- mice, depending on the gene targeting construct and the genetic background, decreased bone mass in P2Y1-/- mice, increased bone mass in P2Y2-/- mice, decreased bone resorption in P2Y6-/- mice, decreased bone...... formation and bone resorption in P2Y13-/- mice. These findings demonstrate the unexpected importance of extracellular nucleotide signalling in the regulation of bone metabolism via multiple P2 receptors and distinct mechanisms involving both osteoblasts and osteoclasts....

  13. A physical mechanism for coupling bone resorption and formation in adult human bone

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Sondergaard, Teis Esben; Skorzynska, Katarzyna Ewa

    2009-01-01

    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone...... within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation...... that osteoclasts and osteoblasts on the bone surface were always covered by a canopy of flat cells expressing osteoblast markers. In contrast, in biopsies in which this canopy was disrupted, bone formation was deficient. Three-dimensional visualizations revealed that this canopy covered the entire remodeling site...

  14. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case

    Directory of Open Access Journals (Sweden)

    Hiromi Yasuda

    2016-11-01

    Full Text Available A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  15. 多发性骨髓瘤骨病临床特点及监测骨代谢标志物的临床意义%Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers

    Institute of Scientific and Technical Information of China (English)

    褚彬; 陆敏秋; 吴梦青; 石磊; 付丽娜; 高珊; 房立娟; 项秋晴; 鲍立

    2016-01-01

    Objective To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers.Methods The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease.The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and β C-terminal telopeptide of type Ⅰ collagen (β-CTX) were monitored regularly in the two years following treatment in 66 cases.Results (1) Among the 178 newly diagnosed MM cases,167 cases complained of pain in bones on first visit,35 cases combined with hypercalcemia,83 cases combined with osteoporosis,154 cases combined with osteolytic bone destruction,and 73 cases combined with pathologic fracture.The most common osteolytic location was the spine.The most common fracture sites was the spine.(2) According to bone disease grading,the 178 cases were divided into group A (bone grade0-2,n=51) and group B(bone grade 3-4,n=127).There were no significant differences between group A and group B in gender,median age,therapeutic effect/ineffec,median overall survival,median progress-free survival,mean serum lactic dehydrogenase,mean albumin,urine light chains and serum creatinine (all P > 0.05).Compared with group A,group B had lower hemoglobin level [(99.78 ± 29.93) vs (108.84 ± 29.30) g/L],and higher blood calcium level [(2.47 ± 0.40) vs (2.30 ± 0.29) mmol/L],serum β2-microglobuin level[(6.04 ±4.84)vs (4.12 ±3.97)mg/L],and bone marrow plasma cells percentage(33.30% ± 24.87% vs 23.51% ± 22.67%) (all P < 0.05).(3) Before treatment,the levels of β-CTX and tPINP in patients of group B (n =47) were higher than those in group A (n =19) (median 0.78 vs 0.42 μg/L,60.95 vs 43.47 μg/L,both P <0.05).The ratio of

  16. Characterization of enzootic foci of Venezuelan equine encephalitis virus in western Venezuela.

    Science.gov (United States)

    Barrera, R; Torres, N; Freier, J E; Navarro, J C; García, C Z; Salas, R; Vasquez, C; Weaver, S C

    2001-01-01

    The distribution of the sylvatic subtype ID Venezuelan equine encephalitis (VEE) viruses in the lowland tropical forests of western Venezuela was investigated using remote sensing and geographic information system technologies. Landsat 5 Thematic Mapper satellite imagery was used to study the reflectance patterns of VEE endemic foci and to identify other locations with similar reflectance patterns. Enzootic VEE virus variants isolated during this study are the closest genetic relatives of the epizootic viruses that emerged in western Venezuela during 1992-1993. VEE virus surveillance was conducted by exposing sentinel hamsters to mosquito bites and trapping wild vertebrates in seven forests identified and located by means of the satellite image. We isolated VEE viruses from 48 of a total of 1,363 sentinel hamsters in two of the forests on six occasions, in both dry and wet seasons. None of the 12 small vertebrates captured in 8,190 trap-nights showed signs of previous VEE virus infection. The satellite image was classified into 13 validated classes of land use/vegetation using unsupervised and supervised techniques. Data derived from the image consisted of the raw digital values of near- and mid-infrared bands 4, 5, and 7, derived Tasseled Cap indices of wetness, greenness, and brightness, and the Normalized Difference Vegetation Index. Digitized maps provided ancillary data of elevation and soil geomorphology. Image enhancement was applied using Principal Component Analysis. A digital layer of roads together with georeferenced images was used to locate the study sites. A cluster analysis using the above data revealed two main groups of dense forests separated by spectral properties, altitude, and soil geomorphology. Virus was isolated more frequently from the forest type identified on flat flood plains of main rivers rather than the forest type found on the rolling hills of the study area. The spatial analysis suggests that mosquitoes carrying the enzootic viruses

  17. Multiple myeloma: 45 cases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hee Chul; Suh, Jin Suck; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1990-10-15

    We evaluated 45 cases of multiple myelomas retrospectively confirmed in Severance Hospital from the period of 1983-1989. In order to assess the radiologic features of the multiple myeloma and to assist in possible early diagnosis and treatment. The result were as follows: 1. IgG(41%) was the most common immunoglobulin type secreted followed by light chain(36%). IgA(19%) and IgD(2%). Two percent of the patients had non-secretory type. 89% of patients were in their stage III of the disease. 2. Among the 45 patients, 96% had abnormal plain radiographic findings with average number of 4.5 lesions. Common sites were the spine, rib, skull, pelvis, and humerus in descending orders. The findings were localized or diffuse osteolytic bone destruction(85%). osteoporosis(49%), pathologic fracture and endosteal scalloping(55%). Osteoporosis was more prominent in stage III than stage II. 3. Both plain X-ray and radioisotope study was available for comparison in 28 patients. Concordance between the two studies were 44%, lesions detected only on plain X-ray film were 51%, and lesions detected only on the radioisotope were 5%. The plain radiography was able to detect only 54% of bone lesions confirmed by bone marrow biopsy. With the above results, accurate evaluation of bone lesions in multiple myeloma may be difficult with radiologic studies only. But familiarity with these radiologic findings of the this disease entity is necessary for early suspicion of the disease, thus for early diagnosis and treatment.

  18. Quantitative analysis of liver GST-P foci promoted by a chemical mixture of hexachlorobenzene and PCB 126: implication of size-dependent cellular growth kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yasong [Colorado State University, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Fort Collins, CO (United States); Translational Pharmacology Group, PDM, Pfizer Inc, Groton, CT (United States); Lohitnavy, Manupat; Lohitnavy, Ornrat; Eickman, Elizabeth; Gerjevic, Lisa; Yang, Raymond S.H. [Colorado State University, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Fort Collins, CO (United States); Reddy, Micaela [DMPK Group, Preclinical Sciences, Roche Palo Alto LLC, CA (United States); Ashley, Amanda [Colorado State University, Department of Cell and Molecular Biology, Fort Collins, CO (United States); Xu, Yihua [University of Wisconsin, McArdle Laboratory for Cancer Research, Madison, WI (United States); Conolly, Rory B. [USEPA, National Center for Computational Toxicology, Research Triangle Park, NC (United States)

    2008-02-15

    The objectives of this study were twofold: (1) evaluating the carcinogenic potential of the mixture of two persistent environmental pollutants, hexachlorobenzene (HCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126), in an initiation-promotion bioassay involving the development of {pi} glutathione S-transferase (GST-P) liver foci, and (2) analyzing the GST-P foci data using a biologically-based computer model (i.e., clonal growth model) with an emphasis on the effect of focal size on the growth kinetics of initiated cells. The 8-week bioassay involved a series of treatments of initiator, two-thirds partial hepatectomy, and daily oral gavage of the mixture of two doses in male F344 rats. The mixture treatment significantly increased liver GST-P foci development, indicating carcinogenic potential of this mixture. Our clonal growth model was developed to simulate the appearance and development of initiated GST-P cells in the liver over time. In the model, the initiated cells were partitioned into two subpopulations with the same division rate but different death rates. Each subpopulation was further categorized into single cells, mini- (2-11 cells), medium- (12-399 cells), and large-foci (>399 cells) with different growth kinetics. Our modeling suggested that the growth of GST-P foci is size-dependent; in general, the larger the foci, the higher the rate constants of division and death. In addition, the modeling implied that the two doses promoted foci development in different manners even though the experimental foci data appeared to be similar between the two doses. This study further illustrated how clonal growth modeling may facilitate our understanding in chemical carcinogenic process. (orig.)

  19. Diffuse Hepatic and Spleen Uptake of Tc-99m MDP on Bone Scintigraphy Resembling Liver-Spleen Scintigraphy in a Patient of Plasma Cell Tumor.

    Science.gov (United States)

    Ravanbod, Mohammad Reza; Nemati, Reza; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid

    2014-01-01

    The present case demonstrates a diffuse intense hepatic and, to a lesser degree, spleen, Tc-99m MDP uptake on a routine bone scintigraphy resembling liver-spleen imaging. A 49-year-old female with a history of anaplastic plasma cell tumor and suffering from bone pain was referred for bone scintigraphy to evaluate possible bone metastases. The bone scintigraphy showed diffuse hepatic and spleen uptake of Tc-99m MDP resembling liver-spleen imaging. Furthermore, bone uptake of Tc-99m MDP was significantly diminished and there were no abnormal foci throughout the skeleton. The bone scintigraphy of the present case of an anaplastic plasma cell tumor suggests the possible presence of amyloidosis.

  20. Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features

    Energy Technology Data Exchange (ETDEWEB)

    Kornaat, Peter R.; Sharma, Ruby; Bloem, Johan L.; Watt, Iain [Leiden University Medical Center, Department of Radiology, Leiden (Netherlands); Kloppenburg, Margreet; Botha-Scheepers, Stella A. [Leiden University Medical Center, Department of Rheumatology, Leiden (Netherlands); Hellio le Graverand, Marie-Pierre [Pfizer Groton, Groton, CT (United States); Coene, L.N.J.E.M. [Haga Hospital, Department of Orthopaedic Surgery, The Hague (Netherlands)

    2007-12-15

    It has been suggested that bone marrow edema-like (BME) lesions in the knee are associated with progression of osteoarthritis (OA). The purpose of our study in patients with OA was to evaluate prospectively changes of BME lesions over 2 years and their relationship with clinical features. Magnetic resonance (MR) images of the knee were obtained from 182 patients (20% male; aged 43-76 years; mean age 59 years) who had been diagnosed with familial symptomatic OA at multiple joint sites. MR images were made at baseline and at 2 years follow-up. BME lesions in 2 years were associated with clinical features assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. A total of 327 BME lesions were recorded. Total size of BME lesions changed in 90 patients (66%). Size of individual lesions changed in 147 foci (45%): new lesions appeared in 69 (21%), existing lesions disappeared in 32 (10%), increased in size in 26 (8%) and decreased in size in 20 (6%) lesions. Increase or decrease of BME lesions, over a 2-year time period, was not associated with severity of WOMAC scores. BME lesions fluctuated in the majority of patients with OA over a 2-year time period. These changes were not associated with severity of WOMAC scores at the study end point. (orig.)

  1. Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features

    Science.gov (United States)

    Kloppenburg, Margreet; Sharma, Ruby; Botha-Scheepers, Stella A.; Le Graverand, Marie-Pierre Hellio; Coene, L. Napoleon J. E. M.; Bloem, Johan L.; Watt, Iain

    2007-01-01

    It has been suggested that bone marrow edema-like (BME) lesions in the knee are associated with progression of osteoarthritis (OA). The purpose of our study in patients with OA was to evaluate prospectively changes of BME lesions over 2 years and their relationship with clinical features. Magnetic resonance (MR) images of the knee were obtained from 182 patients (20% male; aged 43–76 years; mean age 59 years) who had been diagnosed with familial symptomatic OA at multiple joint sites. MR images were made at baseline and at 2 years follow-up. BME lesions in 2 years were associated with clinical features assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. A total of 327 BME lesions were recorded. Total size of BME lesions changed in 90 patients (66%). Size of individual lesions changed in 147 foci (45%): new lesions appeared in 69 (21%), existing lesions disappeared in 32 (10%), increased in size in 26 (8%) and decreased in size in 20 (6%) lesions. Increase or decrease of BME lesions, over a 2-year time period, was not associated with severity of WOMAC scores. BME lesions fluctuated in the majority of patients with OA over a 2-year time period. These changes were not associated with severity of WOMAC scores at the study end point. PMID:17823802

  2. Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats

    Directory of Open Access Journals (Sweden)

    Rodrigues M.A.M.

    2002-01-01

    Full Text Available Aberrant crypt foci (ACF in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks and medium-term (30 weeks assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks assay.

  3. Detectability of metastatic bone tumor by Ga-67 scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Koizumi, Kiyoshi; Uchiyama, Guio; Araki, Tsutomu; Hihara, Toshihiko; Ogata, Hitoshi; Monzawa, Shuichi; Kachi, Kenji; Matsusako, Masaki

    1989-03-01

    Ga-67 scintigrams in patients with malignant diseases sometimes reveal uptake of the tracer in the bone metastases. Detectability of Ga-67 scintigraphy for metastatic bone tumors and benign bone lesions was compared with that of Tc-99m bone scintigraphy. Countable bone metastases detected by bone scintigraphy were evaluated whether the lesion showed apparent, faint, or negative Ga-67 uptake. Of 47 lesions 23 (49%) showed apparent uptake and 17 (36%) showed negative uptake, only 7 (10%) mostly fracture/osteotomy, showed apparent uptake of the tracer. Uptake in the other benign lesions such as trauma of the ribs, spondylosis deformans, and arthrosis deformans was rather faint. In patients with multiple bone metastases, 9 patients (82%) out of 11 showed more prominent abnormal findings in Tc-99m MDP bone scintigraphy than in Ga-67 scintigraphy; that is, Ga-67 scintigraphy was not able to reveal all metastatic bone lesions. In patients with untreated or recurrent tumors, relation between Ga-67 uptake in the tumors and that in the bone metastases was evaluated. Of 7 patients with negative Ga-67 uptake in the bone metastases; that is, there seemed to be little relation between Ga-67 affinity to the primary tumors and that to the bone metastases. Mechanisms of the Ga-67 uptake in the bone metastases were discussed. Not only the tumor cells or tissues in the bone metastases but also bone mineral or osteoclasts might be the deposition sites of Ga-67.

  4. Atypical manifestations of multiple myeloma: Radiological appearance

    Energy Technology Data Exchange (ETDEWEB)

    Hess, Thomas [Department of Radiology, St-Vincenz Hospital, Auf dem Schafsberg, D-65549 Limburg (Germany)]. E-mail: t.hess@st-vincenz.de; Egerer, Gerlinde [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kasper, Bernd [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Rasul, Kakil Ibrahim [Hamad Medical Center, Moha (Qatar); Goldschmidt, Hartmut [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kauffmann, G.W. [Department of Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany)

    2006-05-15

    Diagnostic procedures performed on patients with multiple myeloma typically reveal lytic bone lesions, osteopenia or osteoporosis, bone marrow infiltration by plasma cells as well as overproduction of immunoglobulin or light chains in the serum or urine. Skeletal manifestations are extremely variable and the unusual forms have been described extensively. Extramedullary plasma-cell tumours (plasmocytoma) are found in about 5% of newly diagnosed patients with multiple myelomas. In this paper we present eight patients with atypical forms of multiple myeloma.

  5. Foci of chronic circumscribed osteomyelitis (Brodie's abscess) that traverse the epiphyseal plate.

    Science.gov (United States)

    Bogoch, E; Thompson, G; Salter, R B

    1984-03-01

    We observed six children who presented with chronic circumscribed osteomyelitis involving the adjacent metaphysis and epiphysis of a long bone, communicating through and damaging the growth cartilage of the epiphyseal plate. Four of the six children were less than or equal to 10 years of age. All six patients presented with the mild symptoms and subtle clinical findings that are characteristic of "Brodie's abscess," which is usually confined to metaphyseal, or occasionally epiphyseal, bone. Four children were treated with antibiotics and by surgical evacuation of the abscess, with visualization of the defect in the epiphyseal plate. Two children were treated with antibiotics alone, initially by the intravenous route. At follow-up 2-14 years after treatment, all affected children had a normal result without evidence of growth disturbance. There are seven previously reported cases of chronic circumscribed osteomyelitis traversing the epiphyseal plate that resulted in growth disturbance. Based on our experience and that reported in the literature, we believe that the intravenous administration of appropriate antibiotics in high doses, followed by oral antibiotics, is sufficient treatment for some children presenting with this condition. The pathogenic organism is likely to be Staphylococcus aureus. Surgical evacuation of the lesion should be performed for acute osteomyelitis involving the epiphyseal plate, for sinus formation or drainage into a synovial joint, for failure of the patient to respond clinically to nonoperative therapy, and for confirmation of the diagnosis if doubt exists.

  6. Dating of cremated bones

    NARCIS (Netherlands)

    Lanting, JN; Aerts-Bijma, AT; van der Plicht, J; Boaretto, E.; Carmi, I.

    2001-01-01

    When dating unburnt bone, bone collagen, the organic fraction of the bone, is used. Collagen does not survive the heat of the cremation pyre, so dating of cremated bone has been considered impossible. Structural carbonate in the mineral fraction of the bone, however, survives the cremation process.

  7. Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

    Directory of Open Access Journals (Sweden)

    Isam M A Zarroug

    Full Text Available The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010. Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies than Galabat (8,202 flies. In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month, and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month while none of flies were collected in August-October (MBR = 0 bites/person/month. In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month and September 2010 (N = 1,163, MBR = 6,978 bites/person/month, whereas, none appeared in collection from April to

  8. The value of bone marrow biopsy pathological examination in the diagnosis of multiple myeloma%骨髓活检病理检查在多发性骨髓瘤诊断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    杨娣娣; 韩秀蕊; 李艳春; 赵园; 张丽洁; 王九菊; 魏绪仓

    2016-01-01

    Objective :To understand the advantages and disadvantages of bone marrow biopsy pathologi-cal examination in the diagnosis of MM ,define the value of bone marrow biopsy pathology in the diagnosis of MM . Methods :Use bone marrow aspiration - biopsy double specimen surgery ,to get bone marrow biopsy and smears ,a-nalysis bone marrow biopsy and smears of 153 newly diagnosed MM patients ,have a comparative study on bone marrow hyperplasia degree ,myeloma cell infiltration ,proliferation models of plasma cells and myeloma cell mor-phology .Result :The hyperplasia and the sensitivity of MM diagnosis of the bone marrow biopsy ,is significantly higher than that of bone marrow smears ,the two have a significant difference ;the myeloma cell infiltration of bone marrow biopsy is higher than that of the smears ,the difference has statistically significance ;the proliferation mode of plasma cells in bone marrow biopsy are interstitial pattern ,nodular interstitial type commonly ,the myeloma cell morphology in bone marrow smears is mainly immature plasma cell type .Conclusion :Bone marrow biopsy can accu-rately reflect the plasma cells proliferation model ,compare to smears ,can have better reflection on bone marrow hy-perplasia and infiltration degree ,and have better sensitivity than smears on the diagnosis of MM ,however ,the plas-ma cells morphology of bone marrow smears is clear ,features typical ,easily identifiable .Bone marrow smears and biopsy synchronous check can improve the sensitivity and accuracy for MM diagnosis ,which has very important sig-nificance for MM early diagnosis and treatment observation .%目的:探讨骨髓活检在多发性骨髓瘤(MM )诊断与治疗中的价值。方法:采用骨髓抽吸-活检双标本取材法,获取骨髓活检及涂片标本,分析153例初诊 MM 患者的骨髓活检与涂片,对骨髓增生度、骨髓瘤细胞浸润度及浆细胞增殖模式、骨髓瘤细胞形态进行比较研究。结果:骨髓

  9. Multiple Pregnancy

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Multiple Pregnancy Home For Patients Search FAQs Multiple Pregnancy Page ... Multiple Pregnancy FAQ188, July 2015 PDF Format Multiple Pregnancy Pregnancy How does multiple pregnancy occur? What are ...

  10. DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

  11. INHIBITORY EFFECT OF BOSCHNIAKIA ROSSICA ON DEN-INDUCED PRECANCEROUS HEPATIC FOCI AND ITS ANTIOXIDATIVE ACTIVITIES IN RATS

    Institute of Scientific and Technical Information of China (English)

    YIN Zong-zhu; JIN Hai-ling; SHEN Ming-hua; LI Tian-zhu; QUAN Ji-shu

    1999-01-01

    Objective: To investigate the inhibitory effect of Boschniakia rossica(BR) on rat precancerous hepatic foci induced by diethylnitrosamine (DEN) and its antioxidative activities. Methods: The expression of tumor markerplacental form glutathione S-transferase (GST-P), p53 and p21 protein were investigated by immunohistochemistry techniques using ABC method. TNF-α was measured by ELISA and antioxidative activities of SOD, MDA, GSH-Px,GST and CAT were investigated by colorimetric method in rat serum and mitochondria of liver cells. Results: The 500 mg/kg of BR-H2O extract fraction from BR-methanol extract had inhibitory effect on the formation of DEN-induced GST-P-positive foci in rat liver and the expression of mutant p53 and p21 protein was lower than that of hepatic precancerous lesions. The serum TNF-α was increased by the administration of BR extract in the early stage of chemical hepatocarcinogenesis in rat livers. The serum and liver cells mitochondria activities of SOD and GSH-Px rose again in rats administered with BR-H2O extract and the increasing activity of GST and content of MDA in the hepatic precancerous were decreased by the BR-H2O extract. Conclusion: These results indicated that BR-H2O extract has inhibitory effect on DEN-induced precancerous hepatic foci in rats and induced TNF-α production in rats. The antioxidative action was exhibited by the administration of BR-H2O extract in the early stage of chemical hepatocarcinogenesis in rat livers.

  12. The p150 subunit of CAF-1 causes association of SUMO2/3 with the DNA replication foci

    Energy Technology Data Exchange (ETDEWEB)

    Uwada, Junsuke [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Global COE (Centers of Excellence) Program, Global Initiative Center for Pulsed Power Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Tanaka, Niina; Yamaguchi, Yutaro; Uchimura, Yasuhiro [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Shibahara, Kei-ichi [Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima (Japan); Nakao, Mitsuyoshi [Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto (Japan); Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Global COE (Centers of Excellence) Program, Global Initiative Center for Pulsed Power Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan)

    2010-01-01

    The small ubiquitin-related modifier 2/3 (SUMO2/3) can be post-translationally conjugated to a wide variety of proteins constituting chromatin, the platform for genetic and epigenetic regulation. Nevertheless, it is unclear how SUMO2/3 and SUMO2/3-modified proteins are delivered to the chromatin fibers. Here we report that the largest subunit of chromatin assembly factor 1 (CAF-1), human p150, interacts directly and preferentially with SUMO2/3. Amino acid residue of 98-105 in p150 is essential and sufficient for SUMO2/3 interaction. p150-SUMO2/3 interaction coincided with regions that replicate chromatin fibers, because accumulation of the proliferating cell nuclear antigen (PCNA), and incorporation of bromodeoxyuridine (BrdU) were detected at foci co-localized with both p150 and SUMO2/3 during the S-phase in a cell line expressing epitope-tagged p150. Although inhibition of SUMO2/3 expression had only a small effect on p150 deposition on the replication sites, depletion of p150 led to delocalization of SUMO2/3 from the replication foci. Furthermore, p150 mutants deficient in SUMO2/3 interaction, caused a major reduction of SUMO2/3 at the replication foci. Thus, our findings suggest an expanded role of p150 as a SUMO2/3-interacting factor, and raise the intriguing possibility that p150 plays a role in promoting delivery of SUMO2/3 or SUMO2/3-modified proteins (or both) on chromatin fibers during replication.

  13. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-03-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  14. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-01-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  15. HDAC inhibitor sodium butyrate sensitizes E1A+Ras-transformed cells to DNA damaging agents by facilitating formation and persistence of γH2AX foci.

    Science.gov (United States)

    Abramova, Maria V; Svetlikova, Svetlana B; Kukushkin, Alexander N; Aksenov, Nikolai D; Pospelova, Tatiana V; Pospelov, Valery A

    2011-12-15

    HDAC inhibitors (HDACi) suppress the growth of tumor cells due to induction of cell cycle arrest, senescence or apoptosis. Recent data demonstrate that HDACi can interfere with DNA Damage Response (DDR) thereby sensitizing the cells to DNA damaging agents. Here, we show that HDACi sodium butyrate (NaBut) potentiates the formation of γH2AX foci predominantly in S-phase E1A+Ras cells. Accumulation of γH2AX foci sensitizes the cells toward such DNA damaging agents as irradiation (IR) and adriamycin. In fact, NaBut potentiates the persistence of γH2AX foci induced by genotoxic agents. The synergizing effects depend on DNA damaging factors and on the order of NaBut treatment. Indeed, NaBut treatment for 24 h leads to an accumulation of G 1-phase cells and a lack of S-phase cells, therefore, adriamycin, a powerful S-phase-specific inhibitor, when added to NaBut-treated cells, is unable to substantially add γH2AX foci. In contrast, IR produces both single- and double-strand DNA breaks at any stage of the cell cycle and was shown to increase γH2AX foci in NaBut-treated cells. Further, a lifetime of IR-induced γH2AX foci depends on the subsequent presence of HDACi. Correspondingly, NaBut withdrawal leads to the extinction of IR-induced γH2AX foci. This necessitates HDACi to hold the IR-induced γH2AX foci unrepaired. However, the IR-induced γH2AX foci persist after long-term NaBut treatment (72 h) even after washing the drug. Thus, although signaling pathways regulating H2AX phosphorylation in NaBut-treated cells remain to be investigated, the obtained results show that NaBut potentiates effects of DNA damaging agents by facilitating formation and persistence of γH2AX foci.

  16. Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal.

    Directory of Open Access Journals (Sweden)

    Lamine Diawara

    Full Text Available BACKGROUND: Mass treatment with ivermectin is a proven strategy for controlling onchocerciasis as a public health problem, but it is not known if it can also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission and test whether ivermectin treatment could be safely stopped in the study areas. METHODOLOGY/PRINCIPAL FINDINGS: Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000. CONCLUSION/SIGNIFICANCE: This study has provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other endemic areas in Africa, the principle of elimination has been established. The African Programme for Onchocerciasis Control has adopted an additional

  17. An automated and highly efficient method for counting and measuring fluorescent foci in rod-shaped bacteria

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Hansen, Flemming G.

    2010-01-01

    P>Direct measurements of cells from photo micrographs are becoming increasingly used when investigating the position and/or distribution of chromosomal loci in bacteria. In general, these measurements have been done manually, and without clear definition of how they are made. Here we present...... a procedure for standardizing the measurement of cell properties from phase contrast images. Furthermore, we present a program using these standardized methods that can measure the intracellular positions of fluorescent foci in bacterial cells faster and with more precision than manual measurement....

  18. Is central benzodiazepine receptor imaging useful for the identification of epileptogenic foci in localization-related epilepsies?

    Energy Technology Data Exchange (ETDEWEB)

    Goethals, Ingeborg; Van de Wiele, Christophe; Dierckx, Rudi [Division of Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent (Belgium); Boon, Paul [Department of Neurology, Ghent University Hospital, Ghent (Belgium)

    2003-02-01

    In the presurgical evaluation of patients with partial epilepsies, the most extensively studied functional neuro-imaging modality to define the origin of seizure onset is fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Generally, this technique reveals a widespread zone of interictal glucose hypometabolism in the region of the epileptogenic focus. However, the technique may miss the epileptogenic region and FDG PET abnormalities may extend beyond the seizure onset zone. Consequently, for the precise identification of epileptogenic regions more specific imaging probes than FDG are warranted. This review considers the clinical utility of iomazenil (IMZ) SPET and flumazenil (FMZ) PET for the precise localization of epileptogenic foci in partial epilepsy syndromes. (orig.)

  19. Multiple sclerosis; Multiple Sklerose

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P. [Universitaet des Saarlandes, Abteilung fuer Diagnostische und Interventionelle Neuroradiologie, Radiologische Klinik, Homburg/Saar (Germany); Shariat, K. [Universitaet des Saarlandes, Klinik fuer Neurochirurgie, Homburg/Saar (Germany); Kostopoulos, P. [Universitaet des Saarlandes, Klinik fuer Neurologie, Homburg/Saar (Germany)

    2008-06-15

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [German] Die Multiple Sklerose (MS) ist die haeufigste chronisch-entzuendliche Erkrankung des Myelins mit eingesprengten Laesionen im Bereich der weissen Substanz des zentralen Nervensystems. Die Magnetresonanztomographie (MRT) hat bei der Diagnosestellung und Verlaufskontrolle eine Schluesselrolle. Dieser Artikel befasst sich mit Hauptcharakteristika der MR-Bildbebung. (orig.)

  20. Use of the γ-H2AX assay to investigate DNA repair dynamics following multiple radiation exposures.

    Directory of Open Access Journals (Sweden)

    Luca G Mariotti

    Full Text Available Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery. In this work, we examined the DNA repair dynamics of cells exposed to radiation delivered in fractions, by assessing the response of histone-2AX (H2AX phosphorylation (γ-H2AX, a marker of DNA double strand breaks. γ-H2AX foci induction and disappearance were monitored following split dose irradiation experiments in which time interval between exposure and dose were varied. Experimental data have been coupled to an analytical theoretical model, in order to quantify key parameters involved in the foci induction process. Induction of γ-H2AX foci was found to be affected by the initial radiation exposure with a smaller number of foci induced by subsequent exposures. This was compared to chromatin relaxation and cell survival. The time needed for full recovery of γ-H2AX foci induction was quantified (12 hours and the 1:1 relationship between radiation induced DNA double strand breaks and foci numbers was critically assessed in the multiple irradiation scenarios.

  1. Smoking and Bone Health

    Science.gov (United States)

    ... supported by your browser. Home Bone Basics Lifestyle Smoking and Bone Health Publication available in: PDF (85 ... late to adopt new habits for healthy bones. Smoking and Osteoporosis Cigarette smoking was first identified as ...

  2. Anorexia nervosa and bone

    National Research Council Canada - National Science Library

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk...

  3. Menopause and Bone Loss

    Science.gov (United States)

    Fact Sheet & Menopause Bone Loss How are bone loss and menopause related? Throughout life your body keeps a balance between the ... lose bone faster than it can be replaced. Menopause—the time when menstrual periods end, which usually ...

  4. The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi (Kawasaki Medical School, Kurashiki, Okayama (Japan))

    1994-06-01

    Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of [sup 99m]Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, [gamma]-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author).

  5. Multifoci Bone Tuberculosis and Lymphadenitis in Mediastinum Mimics Malignancy on FDG-PET/CT: A Case Report

    Directory of Open Access Journals (Sweden)

    Nalan Alan Selçuk

    2014-02-01

    Full Text Available Positron Emission Tomography with 2-deoxy-[F-18]-fluoro-D-glucose (FDG-PET has become a reliable diagnostic tool in clinical practice similar to Magnetic Resonance (MR imaging and Computed Tomography (CT. FDG-PET has especially been used to differentiate malignant from benign lesions, and for staging and follow- up malignant tumors. However, FDG-PET has some pitfalls in cancer screening and FDG tracer accumulates at sites of infection and inflammation. Bone tuberculosis may be confused with malignant tumors of bone and its metastases, and can accumulate focally increased FDG in active period. We present a 60-year-old woman with lytic bone lesions and mediastinal hypermetabolic foci, initially suspected to be malignant by means of FDG-PET and the other imaging modalities; however, bone biopsy confirmed the diagnosis of bone tuberculosis

  6. Dicentric chromosomes and gamma-H2AX foci formation in lymphocytes of human blood samples exposed to a CT scanner: a direct comparison of dose response relationships.

    Science.gov (United States)

    Golfier, Sven; Jost, Gregor; Pietsch, Hubertus; Lengsfeld, Philipp; Eckardt-Schupp, Friederike; Schmid, Ernst; Voth, Matthias

    2009-02-01

    Experiments using the induction of dicentric chromosomes (dicentrics) as well as the gamma-H2AX foci formation in lymphocytes of blood samples from a healthy donor were performed to directly evaluate the radiation sensitivity of both biological endpoints. For computed tomography scans at dose levels from 0.025 to 1 Gy, a linear-quadratic dose-response relationship for dicentrics and a linear dose-response relationship for gamma-H2AX foci were obtained. The coefficients of the dose-response relationship for dicentrics are alpha = (3.76 +/- 0.29) x 10(-2) Gy(-1) and beta = (5.54 +/- 0.45) x 10(-2) Gy(-2), the linear coefficient for gamma-H2AX foci is (7.38 +/- 0.11) Gy(-1). The findings indicate that scoring of dicentrics as well as microscopic analysis of gamma-H2AX foci are sensitive methods to quantify a radiation-induced biological damage at low doses. However, since gamma-H2AX foci can be partially repaired within a few hours, biological damages present for days or even months, which constitute the clinically relevant endpoints, can only be quantified reliably by scoring of chromosome aberrations. Thus currently the quantification of dicentrics or reciprocal translocations remains the recommended method for estimating the effect of exposures to low dose levels of radiation ('biological dosimetry'). However, owing to the high radiation sensitivity of the gamma-H2AX foci assay observed in the present study, further investigations on the effectiveness of low-linear energy transfer radiation qualities in producing gamma-H2AX foci in lymphocytes from healthy donors should be performed.

  7. Induction of foci of altered, γ-glutamyltranspeptidase-positive hepatocytes in carcinogen-treated rats fed a choline-deficient diet

    Science.gov (United States)

    Sells, M. A.; Katyal, S. L.; Sell, S.; Shinozuka, H.; Lombardi, B.

    1979-01-01

    A series of experiments was performed to investigate whether, after exposure of rats to a chemical hepatocarcinogen, feeding a choline-deficient (CD) diet would promote the proliferation of initiated liver cells, and their evolution to foci of altered γ-glutamyltranspeptidase (GGT)-positive hepatocytes, without subjecting the animals to further experimental manipulations. Diethylnitrosamine (DEN), in single doses of 15-150 mg/kg body weight, was injected into male, Sprague-Dawley rats, either intact or 18 h after a partial hepatectomy (PH). The animals were then fed either a CD or a choline-supplemented (CS) diet for 2-8 weeks. Emergence in the liver of foci of altered, GGT+ hepatocytes was studied by histological and histochemical techniques. Foci, in varying numbers, developed in the liver of all rats fed the CD diet. The number of foci induced was larger when DEN was administered after PH rather than to intact rats. Foci developed in none of the livers of rats fed the CS diet, except in one experiment in which 30 mg DEN/kg body weight was injected after a PH. In all cases, foci of altered, GGT+ hepatocytes were shown to be α-foetoprotein after immunofluorescence staining of liver sections. It is concluded that feeding a CD diet exerts a strong promoting action on the proliferation and further evolution of liver cells initiated by a chemical carcinogen, providing the basis for a new and efficient procedure for the induction of foci of altered hepatocytes in rat liver. ImagesFig. 2Fig. 3Fig. 4Fig. 5 PMID:89859

  8. Multiple Intussusceptions Associated with Polycythemia in an Anabolic Steroid Abuser, A Case Report and Literature Review

    OpenAIRE

    Cavanagh, Y.; Shah, N.; Thomas, AB; Gupta, A

    2015-01-01

    Intussusceptions are generally associated with mechanical lead points or localized inflammation that function as foci for intestinal telescoping. We present the case of a patient whose abuse of anabolic steroids resulted in the development of multiple simultaneous intussusceptions. Our patient had no additional identifiable risk factors for intussusception. Consistent with previous reports, corticosteroid induced polycythemia and its consequent hyperviscosity led to intravascular sludging and...

  9. Myeloma bone disease: Pathophysiology and management

    Science.gov (United States)

    Silbermann, Rebecca; Roodman, G. David

    2013-01-01

    Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases tumor growth, directly stimulates the OCL formation, and induces cells in the marrow microenvironment to produce factors that drive OCL formation and suppress OBL formation. Factors produced by marrow stromal cells and OCL promote tumor growth through direct action on myeloma cells and by increasing angiogenesis. Current therapies targeting MMBD focus on preventing osteoclastic bone destruction; however regulators of OBL inhibition in MMBD have also been identified, and targeted agents with a potential anabolic effect in MMBD are under investigation. This review will discuss the mechanisms responsible for MMBD and therapeutic approaches currently in use and in development for the management of MMBD. PMID:26909272

  10. Magnetic resonance imaging of the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Baur-Melnyk, Andrea (ed.) [Klinikum der Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2013-08-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  11. Synthetic bone substitute engineered with amniotic epithelial cells enhances bone regeneration after maxillary sinus augmentation.

    Directory of Open Access Journals (Sweden)

    Barbara Barboni

    Full Text Available BACKGROUND: Evidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined. AIM: In the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC, loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT technique, was evaluated in an animal study. MATERIAL AND METHODS: Two blocks of synthetic bone substitute (∼0.14 cm(3, alone or engineered with 1×10(6 ovine AEC (oAEC, were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.. Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT, morphological, morphometric and biochemical analyses. RESULTS AND CONCLUSIONS: The obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation, data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their

  12. Methylation of C9orf72 expansion reduces RNA foci formation and dipeptide-repeat proteins expression in cells.

    Science.gov (United States)

    Bauer, Peter O

    2016-01-26

    A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), together referred to as c9FTD/ALS. It has been suggested that a loss of C9orf72 protein expression, the formation of toxic RNA foci and dipeptide-repeat proteins contribute to C9orf72-related diseases. Interestingly, it has been shown that trimethylation of histones and methylation of CpG islands near the repeat expansion may play a role in the pathogenesis c9FTD/ALS. Recently, methylation of expanded repeat itself has been reported. To further elucidate the mechanisms underlying these diseases, the influence of epigenetic modification in the repeat expansion on its pathogenic effect was assessed. Here, a reduced formation of toxic RNA foci and dipeptide-repeat proteins upon methylation of the GGGGCC repeat in a cellular model of c9FTD/ALS is shown. Additionally, a novel methylcytosine-capture DNA hybridization immunoassay for semi-quantitative detection of the repeat methylation levels is presented, potentially usable for methylation analysis in patients carrying C9orf72 repeat expansion carriers as a diagnostic tool. Presented results suggest that increased level of pathogenic GGGGCC expansion methylation may be sufficient to alleviate the molecular pathology of the C9orf72-related diseases.

  13. Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.

    Science.gov (United States)

    Bose, A; Elyagoby, A; Wong, T W

    2014-07-01

    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

  14. Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

    Science.gov (United States)

    Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

    2007-01-01

    We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

  15. Multiple Myeloma: Diagnosis and Treatment.

    Science.gov (United States)

    Michels, Thomas C; Petersen, Keith E

    2017-03-15

    Multiple myeloma accounts for 1.6% of all cancer cases and approximately 10% of hematologic malignancies in the United States. In 2015, an estimated 28,850 new cases of multiple myeloma were diagnosed in the United States, and the disease caused more than 11,000 deaths. Patients older than 65 years account for 85% of those diagnosed with multiple myeloma, and there is a twofold increased incidence in blacks compared with whites. Patients may present with bone pain or with symptoms that are often nonspecific, such as nausea, vomiting, malaise, weakness, recurrent infections, and weight loss. Many patients present with only laboratory abnormalities, such as anemia, renal disease, and elevated protein levels. The diagnosis of multiple myeloma requires increased numbers of immature, abnormal, or atypical plasma cells in the bone marrow; a monoclonal protein in the serum or urine; or characteristic bone lesions. The diagnostic workup in a patient with suspected multiple myeloma should include a complete blood count with differential; serum chemistries; creatinine, lactate dehydrogenase, and beta2-microglobulin tests; immunoglobulin studies; skeletal survey; and bone marrow evaluation. Initiation of chemotherapy and assessment of eligibility for autologous stem cell transplantation require referral to an oncologist. Most patients with multiple myeloma will receive thromboprophylaxis, bisphosphonate therapy, and prophylaxis against infection at some point in their treatment. Family physicians play a role in assessing these patients for infection, adverse treatment effects, and renal and thrombotic complications, and in managing issues related to pain, nutrition, and psychosocial support.

  16. Primary bone tumors of the spine.

    Science.gov (United States)

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts.

  17. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors.

    Science.gov (United States)

    Lang, Julien; Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie-Edith

    2012-04-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (γH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of γH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional responses. We further establish the existence, restrictive to the G1/S transition, of specific DSB-induced foci containing tobacco E2F transcription factors, in both A. thaliana roots and BY-2 tobacco cells. These E2F foci partially colocalize with γH2AX foci while their formation is ataxia telangiectasia mutated (ATM)-dependent, requires the E2F transactivation domain with its retinoblastoma-binding site and is optimal in the presence of functional H2AXs. Overall, our results unveil a new interplay between plant H2AX and E2F transcriptional activators during the DSB response.

  18. Trypanosoma vivax, T. congolense “forest type” and T. simiae: prevalence in domestic animals of sleeping sickness foci of Cameroon

    Directory of Open Access Journals (Sweden)

    Nimpaye H.

    2011-05-01

    Full Text Available In order to better understand the epidemiology of Human and Animal trypanosomiasis that occur together in sleeping sickness foci, a study of prevalences of animal parasites (Trypanosoma vivax, T. congolense “forest type”, and T. simiae infections was conducted on domestic animals to complete the previous work carried on T. brucei gambiense prevalence using the same animal sample. 875 domestic animals, including 307 pigs, 264 goats, 267 sheep and 37 dogs were sampled in the sleeping sickness foci of Bipindi, Campo, Doumé and Fontem in Cameroon. The polymerase chain reaction (PCR based method was used to identify these trypanosome species. A total of 237 (27.08% domestic animals were infected by at least one trypanosome species. The prevalence of T. vivax, T. congolense “forest type” and T. simiae were 20.91%, 11.42% and 0.34% respectively. The prevalences of T. vivax and T. congolense “forest type” differed significantly between the animal species and between the foci (p < 0.0001; however, these two trypanosomes were found in all animal species as well as in all the foci subjected to the study. The high prevalences of T. vivax and T. congolense “forest type” in Bipindi and Fontem-Center indicate their intense transmission in these foci.

  19. Understanding Bone Strength Is Not Enough.

    Science.gov (United States)

    Hernandez, Christopher J; van der Meulen, Marjolein Ch

    2017-01-09

    Increases in fracture risk beyond what are expected from bone mineral density (BMD) are often attributed to poor "bone quality," such as impaired bone tissue strength. Recent studies, however, have highlighted the importance of tissue material properties other than strength, such as fracture toughness. Here we review the concepts behind failure properties other than strength and the physical mechanisms through which they cause mechanical failure: strength describes failure from a single overload; fracture toughness describes failure from a modest load combined with a preexisting flaw or damage; and fatigue strength describes failure from thousands to millions of cycles of small loads. In bone, these distinct failure mechanisms appear to be more common in some clinical fractures than others. For example, wrist fractures are usually the result of a single overload, the failure mechanism dominated by bone strength, whereas spinal fractures are rarely the result of a single overload, implicating multiple loading cycles and increased importance of fatigue strength. The combination of tissue material properties and failure mechanisms that lead to fracture represent distinct mechanistic pathways, analogous to molecular pathways used to describe cell signaling. Understanding these distinct mechanistic pathways is necessary because some characteristics of bone tissue can increase fracture risk by impairing fracture toughness or fatigue strength without impairing bone tissue strength. Additionally, mechanistic pathways to failure associated with fracture toughness and fatigue involve multiple loading events over time, raising the possibility that a developing fracture could be detected and interrupted before overt failure of a bone. Over the past two decades there have been substantial advancements in fracture prevention by understanding bone strength and fractures caused by a single load, but if we are to improve fracture risk prevention beyond what is possible now, we must

  20. Characterizing bone marrow involvement in Hodgkin's lymphoma by FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Weiler-Sagie, Michal; Kagna, Olga [Rambam Health Care Campus, Nuclear Medicine Department, Haifa (Israel); Dann, Eldad J. [Rambam Health Care Campus and B. and R. Rappaport Faculty of Medicine, Technion, Hematology Department, Haifa (Israel); Ben-Barak, Ayelet [Rambam Health Care Campus and B. and R. Rappaport Faculty of Medicine, Technion, Pediatric Hemato-Oncology Department, Haifa (Israel); Israel, Ora [Rambam Health Care Campus and B. and R. Rappaport Faculty of Medicine, Technion, Nuclear Medicine Department, Haifa (Israel)

    2014-06-15

    Fluoro-deoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is superior to iliac bone marrow biopsy (iBMB) for detection of bone marrow involvement (BMI) in staging of Hodgkin's lymphoma (HL). The present study aims to characterize the patterns and distribution of BMI in HL as determined by FDG-PET/CT. Reports of FDG-PET/CT studies performed for staging of HL were reviewed. BMI was defined as positive iBMB and/or foci of pathological FDG uptake in the skeleton that behaved in concordance with other sites of lymphoma in studies following chemotherapy. Number of FDG uptake foci, their specific location in the skeleton and the presence of corresponding lesions in the CT component of the study, and stage according to the Ann Arbor staging system, were recorded. The study included 473 patients. iBMB was performed in 336 patients. Nine patients had positive iBMB (9/336, 3 %). Seventy-three patients (73/473, 15 %) had FDG-PET/CT-defined BMI. The BM was the only extranodal site of HL in 52/473 patients (11 %). Forty-five patients had three or more foci of pathological skeletal FDG uptake (45/73, 62 %). Sixty-four patients (64/73, 88 %) had at least one uptake focus in the pelvis or vertebrae. In 60 patients (60/73, 82 %), the number of skeletal FDG uptake foci without corresponding CT lesions was equal to or higher than the number of foci with morphological abnormalities. FDG-PET/CT demonstrated BMI in 15 % of patients with newly diagnosed HL. Diagnosis of BMI in HL by FDG-PET/CT was more sensitive than iBMB with potential upstage in 11 % of patients. The most common pattern of FDG-PET/CT BMI was multifocal (at least three foci) skeletal FDG uptake, with at least one focus in the pelvis or vertebrae and no corresponding CT lesions. (orig.)

  1. Bone Scintigraphic Findings in MRSA Osteomyelitis.

    Science.gov (United States)

    Cornejo, Patricia; Mandell, Gerald A

    2016-02-01

    Methicillin-resistant Staphylococcus aureus osteomyelitis is a severe form of infection characterized by multifocal or multiple segmental osseous involvement and subperiosteal abscess formation with increased frequency of extraosseous complications including pyomyositis, septic thrombus, and septic arthritis. Bone scan showed long segment and/or multifocal involvement in 4 of 5 patients with areas of abnormal increased and decreased uptake. The clinical presentations included limp and/or pain. Joint involvement was seen in 4 cases. Bone scan abnormalities correlated well with MRI findings of severe and extensive bone disease, abscess formation, muscle, as well as joint and soft tissue involvement.

  2. Multiple Myeloma, Version 2.2016

    Science.gov (United States)

    Anderson, Kenneth C.; Alsina, Melissa; Atanackovic, Djordje; Biermann, J. Sybil; Chandler, Jason C.; Costello, Caitlin; Djulbegovic, Benjamin; Fung, Henry C.; Gasparetto, Cristina; Godby, Kelly; Hofmeister, Craig; Holmberg, Leona; Holstein, Sarah; Huff, Carol Ann; Kassim, Adetola; Krishnan, Amrita Y.; Kumar, Shaji K.; Liedtke, Michaela; Lunning, Matthew; Raje, Noopur; Singhal, Seema; Smith, Clayton; Somlo, George; Stockerl-Goldstein, Keith; Treon, Steven P.; Weber, Donna; Yahalom, Joachim; Shead, Dorothy A.; Kumar, Rashmi

    2016-01-01

    Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM. PMID:26553768

  3. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  4. Bone Marrow Diseases

    Science.gov (United States)

    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 ...

  5. Orchestration of bone remodeling

    NARCIS (Netherlands)

    Moester, Martiene Johanna Catharina

    2014-01-01

    In healthy individuals, a balance exists between bone formation and resorption. Disruption of this balance can lead to higher or lower bone mass, and disease such as osteoporosis. Treatment for osteoporosis generally inhibits bone resorption, but does not rebuild bone to a healthy strength. More kno

  6. Bone grafts in dentistry

    Directory of Open Access Journals (Sweden)

    Prasanna Kumar

    2013-01-01

    Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

  7. Bone Health and Osteoporosis.

    Science.gov (United States)

    Lupsa, Beatrice C; Insogna, Karl

    2015-09-01

    Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to decreased bone strength and an increased risk of low-energy fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. Bone loss is an inevitable consequence of the decrease in estrogen levels during and following menopause, but additional risk factors for bone loss can also contribute to osteoporosis in older women. A well-balanced diet, exercise, and smoking cessation are key to maintaining bone health as women age. Pharmacologic agents should be recommended in patients at high risk for fracture.

  8. Disappearance of some human African trypanosomiasis transmission foci in Zambia in the absence of a tsetse fly and trypanosomiasis control program over a period of forty years.

    Science.gov (United States)

    Mwanakasale, Victor; Songolo, Peter

    2011-03-01

    We conducted a situation analysis of human African trypanosomiasis (HAT) in Zambia from January 2000 to April 2007. The aim of this survey was to identify districts in Zambia that were still recording cases of HAT. Three districts namely, Mpika, Chama, and Chipata were found to be still reporting cases of HAT and thus lay in HAT transmission foci in North Eastern Zambia. During the period under review, 24 cases of HAT were reported from these three districts. We thereafter reviewed literature on the occurrence of HAT in Zambia from the early 1960s to mid 1990s. This revealed that HAT transmission foci were widespread in Western, North Western, Lusaka, Eastern, Luapula, and Northern Provinces of Zambia during this period. In this article we have tried to give possible reasons as to why the distribution of HAT transmission foci is so different between before and after 2000 when there has been no active national tsetse fly and trypanosomiasis control program in Zambia.

  9. BONE IN OSTEOPETROSIS

    Directory of Open Access Journals (Sweden)

    Ramkumar

    2014-04-01

    Full Text Available Osteopetrosis, a generalized developmental bone disease due to genetic disturbances, characterized by failure of bone re sorption and continuous bone formation making the bone hard, dense and brittle. Bones of intramembranous ossification and enchondrial ossification are affected genetically and symmetrically. During the process of disease the excess bone formation obliterates the cranial foramina and presses the optic, auditory and facial nerves resulting in defective vision, impaired hearing and facial paralysis. The bone formation in osteopetrosis affects bone marrow function leading to severe anemia and deficient of blood cells. The bone devoid of blood supply due to compression of blood vessels by excess formation of bone are prone to osteomyelitic changes with suppuration and pathological fracture if exposed to infection. Though the condition is chronic progressive, it produces changes leading to fatal condition, it should be studied thoroughly by everyone and hence this article presents a classical case of osteopetrosis with detailed description and discussion for the benefit of readers

  10. Interesting bone scans - unusual findings

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, M.; Wadhwa, S.S.; Mansberg, R.; Fernandes, V.B. [Wollongong Hospital, Wollongong, NSW (Australia)

    1997-12-01

    A 59-year-old female with carcinoma of the colon and known liver metastatic disease was referred for bone scan to evaluate for bone metastases. Although no bone metastases were found, there was abnormal uptake noted in the liver corresponding to a metastatic calcified lesion. The only other findings were of degenerative disease in the cervical spine, right shoulder and small joints of the hands. A 69-year-old male with carcinoma of the prostate and right side low back pain was referred for bone scan. No focal abnormalities to suggest metastatic disease were identified; findings within the cervical spine, lumber spine and knees were presumed secondary to degenerative disease. Intermittent pain persisted and the patient was referred for a repeat bone scan six months later. Previous scan findings of degenerative disease and no metastatic disease were confirmed; however, closer inspection revealed an enlarged right kidney with significant retention of tracer in the pelvicalyceal system suggesting possible obstruction. A Retrograde pyelogram was performed, and no obvious obstruction demonstrated. As bone scan findings were very suggestive of obstruction, a DTPA scan with lasix was performed showing a dilated right collecting system with no functional obstruction. Given the degree of dilation, it is possible that the patient experiences intermittent PUJ obstruction causing his symptoms. A 33-year-old male with insulin dependent diabetes mellitus and viral arthritis was referred for a bone scan. A three phase revealed increased uptake in the region of the knee and leR proximal tibia. Delayed whole body images revealed multiple focal areas of osteoblastic activity in the leR tibia. Abnormal uptake was also seen in the upper third of the leR femur. The remainder of the skeletal survey was normal. X-ray correlation of the leR tibia and femoral findings was undertaken. Combinating unilateral changes on bone scan and X-ray although very suggestive of sclerotic polyostotic

  11. Choline deficient diet enhances the initiating and promoting effects of methapyrilene hydrochloride in rat liver as assayed by the induction of gamma-glutamyltranspeptidase-positive hepatocyte foci.

    Science.gov (United States)

    Perera, M. I.; Katyal, S. L.; Shinozuka, H.

    1987-01-01

    Earlier we demonstrated that short-term feeding of methapyrilene hydrochloride (MPH) and of a choline deficient (CD) diet to rats induced peroxidative damage of microsomal membrane lipids of liver cells. In the present study, we investigated whether a CD diet modifies the extent of MPH-induced lipid peroxidation and whether the modifications lead to changes in the initiating and promoting action of these agents using assays of the induction of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci. Addition of 0.1% MPH to a CD diet enhanced the extent of microsomal lipid peroxidation induced by a CD diet alone. Feeding a choline supplemented (CS) or a CD diet containing 0.1% MPH for 2 weeks followed by 7 weeks promotion by a CD diet plus phenobarbital was ineffective in inducing GGT-positive foci. Feeding MPH in a CS or a CD diet for 4 weeks, however, resulted in the development of substantial numbers of GGT-positive foci. There was a 3 fold increase in the number of foci in rats initiated with a CD + MPH diet over that in rats initiated with a CS + MPH diet. 0.1% MPH in a CS diet or a CD diet exerted significant promotional effects on the induction of GGT-positive foci in rats initiated with a single injection of diethylnitrosamine. Addition of MPH to a CD diet was additive in inducing GGT-positive foci. The results suggest that lipid peroxidation of the liver may be involved in the carcinogenic and/or promoting effects of MPH and a CD diet. PMID:2893639

  12. Novel Image Processing Interface to Relate DSB Spatial Distribution from Immunofluorescence Foci Experiments to the State-of-the-Art Models of DNA Breakage

    Science.gov (United States)

    Ponomarev, A. L.; Cucinotta, F. A.

    2004-01-01

    A recently developed software (NASARadiationTrackImage) allows a quick and automatic segmentation of foci that indicate spatial localization of specific proteins that are visualized by immunofluorescence. Of interest are the spatial and temporal distribution of foci such as gammaH2AX, a signal of the phosphorylation of a variant of the histone H2A that has been shown to correspond to DSBs, or proteins involved in DSB processing, such as ATM, Rad51, and p53, following exposures of human cells to high charge and energy (HZE) ion irradiation. Experimental data are recorded as sets of two-dimensional images in color with cells and foci of gammaH2AX, ATM, Rad51 or others shown. Different cells, levels of radiation and timing after radiation were recorded. The software allows us to calculate the number of foci per cell, overall intensity of light in foci and their spatial organization. A simple statistical model allows for testing of foci overlap (eclipse). A more complex statistical model previously known as DNAbreak simulates track structure and random chromosome geometry. It has one adjustable parameter corresponding to an average intensity of DSB creation in cubic micrometers of DNA volume per particle track or unit dose. Its limitation is the low-resolution limit both in physical space and DSB's along DNA. It works adequately on the scale of a cell and provides further insights on how the geometry of tracks and DNA affects genomic damage of the cell and subsequent repair. Future developments of the model for the description of the time evolution of DNA damage response proteins, and more robust track structure models will be discussed.

  13. γ-H2AX foci are increased in lymphocytes in vivo in young children 1 h after very low-dose X-irradiation: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Halm, Brunhild M.; Franke, Adrian A.; Lai, Jennifer F. [University of Hawaii Cancer Center, Honolulu, HI (United States); Turner, Helen C.; Brenner, David J.; Zohrabian, Vatche M. [Columbia University Medical Center, Center for Radiological Research, New York, NY (United States); DiMauro, Robert [Kapi' olani Medical Center for Women and Children, Honolulu, HI (United States)

    2014-10-15

    Computed tomography (CT) is an imaging modality involving ionizing radiation. The presence of γ-H2AX foci after low to moderate ionizing radiation exposure has been demonstrated; however it is unknown whether very low ionizing radiation exposure doses from CT exams can induce γ-H2AX formation in vivo in young children. To test whether very low ionizing radiation doses from CT exams can induce lymphocytic γ-H2AX foci (phosphorylated histones used as a marker of DNA damage) formation in vivo in young children. Parents of participating children signed a consent form. Blood samples from three children (ages 3-21 months) undergoing CT exams involving very low blood ionizing radiation exposure doses (blood doses of 0.22-1.22 mGy) were collected immediately before and 1 h post CT exams. Isolated lymphocytes were quantified for γ-H2AX foci by a technician blinded to the radiation status and dose of the patients. Paired t-tests and regression analyses were performed with significance levels set at P < 0.05. We observed a dose-dependent increase in γ-H2AX foci post-CT exams (P = 0.046) among the three children. Ionizing radiation exposure doses led to a linear increase of foci per cell in post-CT samples (102% between lowest and highest dose). We found a significant induction of γ-H2AX foci in lymphocytes from post-CT samples of three very young children. When possible, CT exams should be limited or avoided by possibly applying non-ionizing radiation exposure techniques such as US or MRI. (orig.)

  14. The Hedgehog signalling pathway in bone formation

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Philipp Andre; Ling Ye; Ying-Zi Yang

    2015-01-01

    The Hedgehog (Hh) signalling pathway plays many important roles in development, homeostasis and tumorigenesis. The critical function of Hh signalling in bone formation has been identified in the past two decades. Here, we review the evolutionarily conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development, homeostasis and diseases. In the early stages of embryonic limb development, Sonic Hedgehog (Shh) acts as a major morphogen in patterning the limb buds. Indian Hedgehog (Ihh) has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium. Hh signalling is also involved intramembrane ossification. Interactions between Hh and Wnt signalling regulate cartilage development, endochondral bone formation and synovial joint formation. Hh also plays an important role in bone homeostasis, and reducing Hh signalling protects against age-related bone loss. Disruption of Hh signalling regulation leads to multiple bone diseases, such as progressive osseous heteroplasia. Therefore, understanding the signalling mechanisms and functions of Hh signalling in bone development, homeostasis and diseases will provide important insights into bone disease prevention, diagnoses and therapeutics.

  15. Multi-frequency axial transmission bone ultrasonometer.

    Science.gov (United States)

    Tatarinov, Alexey; Egorov, Vladimir; Sarvazyan, Noune; Sarvazyan, Armen

    2014-07-01

    The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis.

  16. Role of bone biopsy in renal osteodystrophy

    Directory of Open Access Journals (Sweden)

    Al Badr Wisam

    2009-01-01

    Full Text Available Renal osteodystrophy (ROD, the abnormal bone histology that occurs in the context of kidney disease, is a disease spectrum and not a uniform progressive bone disease. It is an important component of the broad disturbances of bone and mineral metabolism associated with chronic kidney disease (CKD. There are multiple pathogenetic factors which contribute to the histological abnormalities seen on bone biopsy. The patients with ROD are rarely symp-tomatic in the early stages of CKD. It is also noteworthy that the clinical manifestations are usually preceded by biochemical changes that are insidious and subtle. This makes it difficult for the clinician to suspect the presence of bone and mineral metabolism abnormalities without direct testing. The serum calcium, phosphorus, and alkaline phosphatase levels are usually normal until late in the course of CKD. The main screening test for abnormal bone and mineral metabolism is the measurement of parathyroid hormone which is also somewhat delayed. The clinical signs and symptoms are also challenging to interpret because of their slow and non-specific nature which may include vague, ill-defined, bone aches and pains, and muscle weakness. The gold standard for diagnosis of ROD is bone biopsy with mineralized bone histology after double tetracycline labeling, iron staining and aluminum staining. The currently used histomorphometric descriptions of bone histology are not well integrated clinically and a new nomenclature that is clinically more relevant and useful has been proposed. Additional studies are required to define the spectrum of ROD in the current therapeutic era, and to find clinically useful non-invasive biomarkers to improve the treatment and monitoring of the abnormal bone in the setting of CKD.

  17. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

  18. Effects of astragalus polysaccharides on the proliferation of bone marrow mesenchymal stem cells from patients with multiple myeloma%黄芪多糖干预多发性骨髓瘤患者骨髓间充质干细胞的变化

    Institute of Scientific and Technical Information of China (English)

    杨景柯; 吕丰收; 韩立

    2016-01-01

    BACKGROUND:Bone marrow mesenchymal stem cels can produce a variety of cytokines to provide some support for the growth and proliferation of myeloma cels. OBJECTIVE:To investigate the effects of astragalus polysaccharides on the proliferation of bone marrow mesenchymal stem cels from patients with multiple myeloma and cytokine secretion. METHODS:Bone marrow mesenchymal stem cels were isolated by density gradient centrifugation from the bone marrow of a healthy volunteer and a multiple myeloma patient, and were cultured and identified. Passage 3 bone marrow mesenchymal stem cels were colected, and the growth curve was depicted by the enzyme marker method. MTT method and flow cytometry were used to detect the effects of different concentrations (0.5, 1, 2, 4, 6, 8 g/L) of astragalus polysaccharides on the proliferation and cel cycle of bone marrow mesenchymal stem cels. The expression levels of interleukin-1β and interleukin-6 were detected by ELISA method. RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cels from both the healthy control and multiple myeloma patient showed negative expression of CD34 and positive expression of CD44. The obtained cels from two sources had the characteristics of bone marrow mesenchymal stem cels. Cels from the healthy control had significantly shorter doubling time than those from the myeloma patient. After treated with 1 and 2 g/L astragalus polysaccharide, cel proliferation rate in the multiple myeloma group was significantly higher than that in the healthy control group; after treated with 6 and 8 g/L astragalus polysaccharide, the cel proliferation rate was significantly lower in the multiple myeloma group than in the healthy control group. After treated with 1 g/L astragalus polysaccharide, compared with the healthy control, the proportion of bone marrow mesenchymal stem cels from the multiple myeloma patient in G0/G1 phase was significantly decreased, while the proportions of cels in both S phase and G2/M phase from the

  19. X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

    Directory of Open Access Journals (Sweden)

    Siegfried A Schwab

    Full Text Available PURPOSE: To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM and to estimate foci after FFDM and digital breast-tomosynthesis (DBT using a biological phantom model. MATERIALS AND METHODS: The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified. RESULTS: Median in-vivo foci level/cell was 0.086 (range 0.067-0.116 before and 0.094 (0.076-0.126 after FFDM (p = 0.0004. In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086-0.140 at skin level and 0.035 (range 0.030-0.050 at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040-0.081 at skin level and 0.015 (range 0.006-0.020 at glandular level. CONCLUSION: In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques.

  20. [An assessment of the status of natural foci of Crimean-Congo hemorrhagic fever in the Crimea].

    Science.gov (United States)

    Markeshin, S Ia; Smirnova, S E; Evstaf'ev, I L

    1992-04-01

    The parasitological data and the results of the virological and serological investigations of materials, collected in nature and in the course of study of the immune structure of the population, are indicative of the circulation of CHF virus in the Crimea and the possibility of human infection. Data on spontaneous infection of four species of Ixodes ticks with CHF virus have been confirmed, including the data, obtained for the first time for this region, on the participation of Dermacentor marginatus in this process. The study has revealed, also for the first time, that, together with European brown hares, the natural foci of this infection may be maintained by scilly shrews, common voles and European wood mice. Low activity of the Crimean focus may be the result of active land reclamation, keeping the cattle stalled in most of the stock-breeding farms of the region, as well as a sharp decline in the number of hares at the territories of hunting preserves.

  1. [An evaluation of the status of natural foci of Crimean-Congo hemorrhagic fever in the Crimea].

    Science.gov (United States)

    Markeshin, S Ia; Smirnova, S E; Evstaf'ev, I L

    1991-09-01

    Parasitological data, the results of virological and serological investigations of materials, collected in nature and during the study of the immune structure of the population and indicative of the circulation of CCHF, virus in the Crimea and the possibility of human infection, are presented. The data on the spontaneous CCHF virus infection of 4 tick species belonging to the genus Ixodes have been confirmed, and evidence on the participation of Dermacentor marginatus in this process obtained for the first time in this region. The study has revealed for the first time that, besides European brown hares, scilly shrews, common voles and field mice may contribute to the maintenance of the natural foci of this infection. The low activity of the Crimean focus of CCHF may be the result of the intensive use of land, the widely spread stall-feeding of cattle, as well as a sharp decrease in the number of hares on the territories of hunting preserves.

  2. Role Breadth Self-Efficacy and Foci of Proactive Behavior: Moderating Role of Collective, Relational, and Individual Self-Concept.

    Science.gov (United States)

    Hwang, Pin-Chyuan; Han, Ming-Chuan; Chiu, Su-Fen

    2015-01-01

    This study aims to identify the interactive effect of role breadth self-efficacy (RBSE) and the three levels of self-concept (collective, relational, and individual) in predicting of different foci of proactive behaviors. Results from 259 matched responses from an airline company in Taiwan showed that RBSE had a positive effect on (1) pro-organizational proactive behavior among those with higher collective self-concept, (2) pro-supervisor proactive behavior among those with higher relational self-concept, and (3) pro-self proactive behavior among those with higher individual self-concept. Our findings provide insights into the moderating role of different levels of self-concept on RBSE-proactive behavior process in terms of specific targets or beneficiaries. Further implications for organizational research and practice are discussed.

  3. Endometrioid like yolk sac tumor of the testis with small teratomatous foci: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Prabir Hazarika

    2015-01-01

    Full Text Available I have reported a case of endometrioid like yolk sac tumor of the testis in a 20-year-old boy. Endometrioid like yolk sac tumor is a rare tumor. A few cases have been reported in ovary. In case of male, a case of pure glandular endometrioid like yolk sac tumor is reported in a 43 years male in right undescended testis and another case of abdominal metastasis showing endometrioid pattern from mixed testicular germ cell tumor comprising of teratoma and embryonal carcinoma. My patient was a 20-year-old male presented with painless enlargement of right testis. Grossly the tumor was glistening creamish white with a multicystic appearance. Histopathological examination showed the tumor to be composed of glandular elements resembling early secretory endometrium, foci of keratinized thin squamous epithelium and a single focus of benign cartilage. The glandular elements show immunohistochemical positivity for AFP, cytokeratin 7 (CK7 and epithelial membrane antigen (EMA.

  4. Regional genetic differentiation of Phlebotomus sergenti in three Moroccan foci of cutaneous leishmaniasis caused by Leishmania tropica

    Directory of Open Access Journals (Sweden)

    Yahia H.

    2004-06-01

    Full Text Available Phlebotomus sergenti was identified morphologically in samples from three Moroccan foci of leishmaniasis caused by Leishmania tropica in the provinces of Azilal, Essaouira and Taza. Three primary mitochondrial DNA lineages were identified, and they could be markers for regionally distributed cryptic species. Greater mitochondrial diversity in Azilal indicated that this central province could have been the origin of dispersal of P. sergenti or the zone of secondary contact. All except one of the 21 mitochondrial haplotypes showed a marked regional distribution, and this indicates that vector control would not always be followed by rapid, long-distance reinvasion. Only mitochondrial haplotype SER 18 was a putative marker for long-distance dispersal, for which there is no evidence of human assistance.

  5. Rare occurrence of natural transovarial transmission of dengue virus and elimination of infected foci as a possible intervention method.

    Science.gov (United States)

    Angel, Annette; Angel, Bennet; Joshi, Vinod

    2016-03-01

    Transovarial transmission of dengue virus has been studied in 33 districts of Rajasthan, India. Small proportion (1.09%) of breeding containers positive for the virus and their elimination has been demonstrated as a possible intervention method of disease control. Dengue virus was isolated from individual mosquitoes employing Indirect Fluorescence Antibody Test and Reverse Transcriptase Polymerase Chain Reaction. Out of 1,30,525 containers examined only 1432(1.09%) showed transovarially transmitted virus activity. Elimination of larvae from all the 1432 virus positive containers resulted in substantial control over prospective transmission of dengue. The study highlights rarity of transovarial transmission under natural conditions and sensitizes whether elimination of vertically infected foci could be used as a new intervention method.

  6. [Production of transmission foci for cutaneous leishmaniasis: the case of Pau da Fome, Rio de Janeiro, Brazil].

    Science.gov (United States)

    Kawa, Hélia; Sabroza, Paulo Chagastelles; Oliveira, Rosely Magalhães de; Barcellos, Christovam

    2010-08-01

    This study analyzes the characteristics of one of the main foci for cutaneous leishmaniasis transmission in the city of Rio de Janeiro, Brazil, examining its territorial configuration and the relations with spatial organization processes. An analytical model was applied to the process of occupation and organization of urban space on a local scale, considering the new functions acquired by the spatial elements expressed by different work relations, land use, and land value. The study employed geoprocessing techniques and classification of images obtained by remote sensing, localization of households, and cases of cutaneous leishmaniasis, associated with qualitative data on the historical process of land occupation and use. The analysis detected areas with distinct conditions of vulnerability and showed that changes in these conditions allowed production of the epidemic in a given time period and its subsequent reduction. The study contributes to monitoring of the disease at the local level and application of effective measures for cutaneous leishmaniasis surveillance and control.

  7. RECENT ADVANCES IN PATHO-BIOLOGY OF MYELOMA BONE DISEASE: CLINICOPATHOLOGY AND LITERATURE OF REVIEW

    Directory of Open Access Journals (Sweden)

    Lohit Kumar

    2016-03-01

    Full Text Available Bone disease is a hallmark of multiple myeloma, presenting as lytic lesions associated with bone pain, pathological fractures requiring surgery and/or radiation to bone, spinal cord compression and hypercalcaemia. Increased osteoclastic activity unaccompanied by a compensatory increase in osteoblast function, leading to enhanced bone resorption results in bone disease. The interaction of plasma cells with the bone marrow microenvironment has been shown to play a vital role. Also, interactions of myeloma cells with osteoclasts enhance myeloma growth and survival, and thereby create a vicious cycle leading to extensive bone destruction and myeloma cell expansion.

  8. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

    Science.gov (United States)

    Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

    2011-01-01

    Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfe