Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

PubMed

Jiruska, Premysl; Proks, Jan; Otáhal, Jakub; Mares, Pavel

2007-10-01

Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.

Bone scintigraphy elucidates different metabolic stages of melorheostosis.

PubMed

Izadyar, Sina; Gholamrezanezhad, Ali

2012-01-01

Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3(rd) and 4(th) metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4(th) metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3(rd) left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints.

Bone scintigraphy elucidates different metabolic stages of melorheostosis

PubMed Central

Izadyar, Sina; Gholamrezanezhad, Ali

2012-01-01

Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3rd and 4th metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4th metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3rd left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints. PMID:22514755

Multimodal Imaging of Disease-Associated Pigmentary Changes in Retinitis Pigmentosa

PubMed Central

Schuerch, Kaspar; Marsiglia, Marcela; Lee, Winston; Tsang, Stephen H.; Sparrow, Janet R.

2016-01-01

Purpose Using multiple imaging modalities we evaluated the changes in photoreceptor cells and RPE that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa (RP). Methods In a cohort of 60 RP patients, short-wavelength autofluorescence (SW-AF), near-infrared (NIR)-AF, NIR-reflectance (NIR-R), spectral domain optical coherence tomography (SD-OCT) and color fundus images were studied. Results Central AF rings were visible in both SW-AF and NIR-AF images. Bone spicule pigmentation was non-reflective in NIR-R, hypoautofluorescent with SW-AF and NIR-AF imaging and presented as intraretinal hyperreflective foci in SD-OCT images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone (EZ) band was absent in SD-OCT scans and the visibility of choroidal vessels in SW-AF, NIR-AF and NIR-R images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch’s membrane thinning became apparent in SD-OCT scans. Conclusions These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread, undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming. PMID:28005673

MULTIMODAL IMAGING OF DISEASE-ASSOCIATED PIGMENTARY CHANGES IN RETINITIS PIGMENTOSA.

PubMed

Schuerch, Kaspar; Marsiglia, Marcela; Lee, Winston; Tsang, Stephen H; Sparrow, Janet R

2016-12-01

Using multiple imaging modalities, we evaluated the changes in photoreceptor cells and retinal pigment epithelium (RPE) that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa. In a cohort of 60 patients with retinitis pigmentosa, short-wavelength autofluorescence, near-infrared autofluorescence (NIR-AF), NIR reflectance, spectral domain optical coherence tomography, and color fundus images were studied. Central AF rings were visible in both short-wavelength autofluorescence and NIR-AF images. Bone spicule pigmentation was nonreflective in NIR reflectance, hypoautofluorescent with short-wavelength autofluorescence and NIR-AF imaging, and presented as intraretinal hyperreflective foci in spectral domain optical coherence tomography images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone band was absent in spectral domain optical coherence tomography and the visibility of choroidal vessels in short-wavelength autofluorescence, NIR-AF, and NIR reflectance images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch membrane thinning became apparent in spectral domain optical coherence tomography. These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming.

SKELETAL DYNAMICS IN MAN MEASURED BY NONRADIOACTIVE STRONTIUM

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

Eisenberg, E.; Gordan, G.S.

Skeletal dynamics were calculated by usual dilution formulas, using stable strontium as a tracer, in 25 normal subjects, 14 athletes, 26 patients with postmenopausal osteoporosis, 28 with primary hyperparathyroidism, 3 with hyperadrenocorticism 8 with acromegaly, 7 with thyrotoxicosis, 11 with urclithiasis, 5 with Paget's disease of bone. and 1 with vitamin D poisoning. The technic requires that 10 mEq of strontium gluconate be injected intravenously and blood and urine concentrations be measured for 4 to 6 days. In normal subjects the rapidly miscible pool was equivalent to 42.7 + 1.1 L of serum, turning over at a rate of 13.5more » plus or minus 0.6 L daily, of which 3.9 + 0.2 L was excreted by the kidney and 9.6 + 0.4 L went to bone. Since only approximately 2.5% of the pool is excreted in the feces daily, fecal excretion was not measured routinely. Good reproducibility was found in 21 duplicate studies. Intense muscular exercise (athletes) was found to expand the pool greatly and to accelerate the rate of deposition in bone. Kinetically, two divergent types of osteoporosis were differentiated. A small pool and low rate of bone deposition were found in postmenopausal osteoporosis and Cushing's disease of long duration. The large pool and rapid rate of bone deposition in thyrotoxicosis was confirmed and also found in acromegaly. In these two, excessive bone resorption is postulated. Urinary excretion rate was excessive in Cushing's disease, thyrotoxicosis, and acromegaly. In hyperparathyroidism with clinically evident osteitis, expanded pools, greatly increased turnover, urinary excretion, and bone deposition rates were confirmed. In patients with normal roentgenographic appearance and phosphatase, bone involvement was shown by slight increase in bone deposition rate and microscopic foci of resorption on iliac crest biopsy. In seven patients without histological foci of resorption, the bone deposition rate was not increased. (auth)« less

Microfluidic co-culture platform for investigating osteocyte-osteoclast signalling during fluid shear stress mechanostimulation.

PubMed

Middleton, K; Al-Dujaili, S; Mei, X; Günther, A; You, L

2017-07-05

Bone cells exist in a complex environment where they are constantly exposed to numerous dynamic biochemical and mechanical stimuli. These stimuli regulate bone cells that are involved in various bone disorders, such as osteoporosis. Knowledge of how these stimuli affect bone cells have been utilised to develop various treatments, such as pharmaceuticals, hormone therapy, and exercise. To investigate the role that bone loading has on these disorders in vitro, bone cell mechanotransduction studies are typically performed using parallel plate flow chambers (PPFC). However, these chambers do not allow for dynamic cellular interactions among different cell populations to be investigated. We present a microfluidic approach that exposes different cell populations, which are located at physiologically relevant distances within adjacent channels, to different levels of fluid shear stress, and promotes cell-cell communication between the different channels. We employed this microfluidic system to assess mechanically regulated osteocyte-osteoclast communication. Osteoclast precursors (RAW264.7 cells) responded to cytokine gradients (e.g., RANKL, OPG, PGE-2) developed by both mechanically stimulated (fOCY) and unstimulated (nOCY) osteocyte-like MLO-Y4 cells simultaneously. Specifically, we observed increased osteoclast precursor cell densities and osteoclast differentiation towards nOCY. We also used this system to show an increased mechanoresponse of osteocytes when in co-culture with osteoclasts. We envision broad applicability of the presented approach for microfluidic perfusion co-culture of multiple cell types in the presence of fluid flow stimulation, and as a tool to investigate osteocyte mechanotransduction, as well as bone metastasis extravasation. This system could also be applied to any multi-cell population cross-talk studies that are typically performed using PPFCs (e.g. endothelial cells, smooth muscle cells, and fibroblasts). Copyright © 2017 Elsevier Ltd. All rights reserved.

Gamma knife treatment for refractory epilepsy in seizure focus localized by positron emission tomography/CT★

PubMed Central

Bai, Xia; Wang, Xuemei; Wang, Hongwei; Zhao, Shigang; Han, Xiaodong; Hao, Linjun; Wang, Xiangcheng

2012-01-01

A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The foci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser’s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser’s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser’s classification score was significantly higher in the single-focus group as compared with the multiple-foci group. PMID:25317147

Diverse bone scan abnormalitites in "shin splints".

PubMed

Spencer, R P; Levinson, E D; Baldwin, R D; Sziklas, J J; Witek, J T; Rosenberg, R

1979-12-01

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of the foot.

Digitally switchable multi-focal lens using freeform optics.

PubMed

Wang, Xuan; Qin, Yi; Hua, Hong; Lee, Yun-Han; Wu, Shin-Tson

2018-04-16

Optical technologies offering electrically tunable optical power have found a broad range of applications, from head-mounted displays for virtual and augmented reality applications to microscopy. In this paper, we present a novel design and prototype of a digitally switchable multi-focal lens (MFL) that offers the capability of rapidly switching the optical power of the system among multiple foci. It consists of a freeform singlet and a customized programmable optical shutter array (POSA). Time-multiplexed multiple foci can be obtained by electrically controlling the POSA to switch the light path through different segments of the freeform singlet rapidly. While this method can be applied to a broad range of imaging and display systems, we experimentally demonstrate a proof-of-concept prototype for a multi-foci imaging system.

Juvenile Osteochondritis Dissecans: Correlation Between Histopathology and MRI.

PubMed

Zbojniewicz, Andrew M; Stringer, Keith F; Laor, Tal; Wall, Eric J

2015-07-01

The objective of our study was to correlate specimens of juvenile osteochondritis dissecans (OCD) lesions of the knee to MRI examinations to elucidate the histopathologic basis of characteristic imaging features. Five children (three boys and two girls; age range, 12-13 years old) who underwent transarticular biopsy of juvenile OCD lesions of the knee were retrospectively included in this study. Two radiologists reviewed the MRI examinations and a pathologist reviewed the histopathologic specimens and recorded characteristic features. Digital specimen photographs were calibrated to the size of the respective MR image with the use of a reference scale. Photographs were rendered semitransparent and over-laid onto the MR image with the location chosen on the basis of the site of the prior biopsy. A total of seven biopsy specimens were included. On MRI, all lesions showed cystlike foci in the subchondral bone, bone marrow edema pattern on proton density-or T2-weighted images, and relatively thick unossified epiphyseal cartilage. In four patients, a laminar signal intensity pattern was seen, and two patients had multiple breaks in the subchondral bone plate. Fibrovascular tissue was found at histopathology in all patients. Cleft spaces near the cartilage-bone interface and were seen in all patients while chondrocyte cloning was present in most cases. Focal bone necrosis and inflammation were infrequent MRI findings. Precise correlation of the MRI appearance to the histopathologic overlays consistently was found. A direct correlation exists between the histopathologic findings and the MRI features in patients with juvenile OCD. Additional studies are needed to correlate these MRI features with juvenile OCD healing success rates.

Diverse bone scan abnormalities in shin splints

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

Spencer, R.P.; Levinson, E.D.; Baldwin, R.D.

1979-12-01

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of themore » foot.« less

Multi-focal multiphoton lithography.

PubMed

Ritschdorff, Eric T; Nielson, Rex; Shear, Jason B

2012-03-07

Multiphoton lithography (MPL) provides unparalleled capabilities for creating high-resolution, three-dimensional (3D) materials from a broad spectrum of building blocks and with few limitations on geometry, qualities that have been key to the design of chemically, mechanically, and biologically functional microforms. Unfortunately, the reliance of MPL on laser scanning limits the speed at which fabrication can be performed, making it impractical in many instances to produce large-scale, high-resolution objects such as complex micromachines, 3D microfluidics, etc. Previously, others have demonstrated the possibility of using multiple laser foci to simultaneously perform MPL at numerous sites in parallel, but use of a stage-scanning system to specify fabrication coordinates resulted in the production of identical features at each focal position. As a more general solution to the bottleneck problem, we demonstrate here the feasibility for performing multi-focal MPL using a dynamic mask to differentially modulate foci, an approach that enables each fabrication site to create independent (uncorrelated) features within a larger, integrated microform. In this proof-of-concept study, two simultaneously scanned foci produced the expected two-fold decrease in fabrication time, and this approach could be readily extended to many scanning foci by using a more powerful laser. Finally, we show that use of multiple foci in MPL can be exploited to assign heterogeneous properties (such as differential swelling) to micromaterials at distinct positions within a fabrication zone.

Central giant cell granuloma in pediatric maxilla: surgical management.

PubMed

Faverani, Leonardo Perez; Ferreira, Sabrina; Ferreira, Gabriel Ramalho; Coléte, Juliana Zorzi; Aranega, Alessandra Marcondes; Garcia Júnior, Idelmo Rangel

2014-07-01

Central giant cell granuloma (CGCG) is an intraosseous lesion consisting of fibrous cellular tissue that contains multiple foci of hemorrhage, multinucleated giant cells, and occasional trabeculae of woven bone. An 8-year-old boy presented himself complaining of a painless swelling in the left maxilla that had started 1 year. Computed tomography (CT) scan confirmed a poorly defined multilocular radiolucent lesion in the left maxilla crossing the midline. The patient underwent enucleation through an intraoral approach of the lesion. The biopsy revealed multinucleated giant cells in a fibrous stroma. A CT was taken approximately 1 year postoperatively. There was no clinical or radiographic evidence of recurrence. Therefore, surgical treatment of CGCG can be performed, trying to preserve the surrounding anatomic structures, which can be maintained in case the lesion does not show an aggressive clinical behavior, avoiding large surgical defects which are undesirable in children.

Distribution of magnesium in central nervous system tissue, trabecular and cortical bone in rats fed with unbalanced diets of minerals.

PubMed

Yasui, M; Yano, I; Yase, Y; Ota, K

1990-11-01

Recent epidemiological changes in patterns of foci of amyotrophic lateral sclerosis (ALS) in the Western Pacific suggest that environmental factors play a contributory role in the pathogenic process of this disorder. In this experimental study on rats, a similar situation of dietary mineral imbalance was created as is found in the soil and drinking water of these ALS foci with a low content of calcium (Ca) and magnesium (Mg) and a high content of aluminum (Al). In groups of rats fed a low Ca diet, low Ca-Mg diet, and low Ca-Mg plus high Al diet, serum Ca levels were found to be lower than those in a group fed a standard diet. Also, serum Mg levels were lower in the groups fed a low Ca-Mg diet and a low Ca-Mg plus high Al diet than in the groups fed a standard diet and only a low Ca diet. There was no significant difference in Mg content of central nervous system (CNS) tissues of groups fed unbalanced and standard diets, except for a significant decrease in Mg content of the spinal cord of rats fed a low Ca-Mg plus high Al diet. Mg content of the lumbar spine and cortical bone decreased in the unbalanced diet groups compared with that of a group fed a standard diet. These findings suggest that under the disturbed bone mineralization induced by unbalanced mineral diets, Mg may be mobilized from bone to maintain the level necessary for vital activity in soft tissues including CNS tissue.

Saccular function in otosclerosis patients: bone conducted-vestibular evoked myogenic potential analysis.

PubMed

Amali, Amin; Mahdi, Parvane; Karimi Yazdi, Alireza; Khorsandi Ashtiyani, Mohammad Taghi; Yazdani, Nasrin; Vakili, Varasteh; Pourbakht, Akram

2014-01-01

Vestibular involvements have long been observed in otosclerotic patients. Among vestibular structures saccule has the closest anatomical proximity to the sclerotic foci, so it is the most prone vestibular structure to be affected during the otosclerosis process. The aim of this study was to investigate the saccular function in patients suffering from otosclerosis, by means of Vestibular Evoked Myogenic Potential (VEMP). The material consisted of 30 otosclerosis patients and 20 control subjects. All participants underwent audiometric and VEMP testing. Analysis of tests results revealed that the mean values of Air-Conducted Pure Tone Average (AC-PTA) and Bone-Conducted Pure Tone Average (BC-PTA) in patients were 45.28 ± 15.57 and 19.68 ± 10.91, respectively and calculated 4 frequencies Air Bone Gap (ABG) was 25.64 ± 9.95. The VEMP response was absent in 14 (28.57%) otosclerotic ears. A statistically significant increase in latency of the p13 was found in the affected ears (P=0.004), differences in n23 latency did not reach a statistically significant level (P=0.112). Disparities in amplitude of p13-n23 in between two study groups was statistically meaningful (P=0.009), indicating that the patients with otosclerosis had lower amplitudes. This study tends to suggest that due to the direct biotoxic effect of the materials released from the otosclerosis foci on saccular receptors, there might be a possibility of vestibular dysfunction in otosclerotic patients.

Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis

PubMed Central

Ferreira, Diego dos Santos; Boratto, Fernanda Alves; Cardoso, Valbert Nascimento; Serakides, Rogéria; Fernandes, Simone Odília; Ferreira, Lucas Antônio Miranda; Oliveira, Mônica Cristina

2015-01-01

Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis) in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis-bearing animals for all investigated time intervals. Biodistribution studies were also performed after the intravenous administration of the formulation in osteomyelitis-bearing animals. A significant amount of liposomes were taken up by the organs of the mononuclear phagocyte system (liver and spleen). Intense renal excretion was also observed during the entire experiment period. Moreover, the liposome uptake by the infectious focus was significantly high. These results show that long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime have a tropism for infectious foci. PMID:25848262

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates.

PubMed

Ashley, T; Plug, A W; Xu, J; Solari, A J; Reddy, G; Golub, E I; Ward, D C

1995-10-01

Antibodies against human Rad51 protein were used to examine the distribution of Rad51 on meiotic chromatin in mouse spermatocytes and oocytes as well as chicken oocytes during sequential stages of meiosis. We observed the following dynamic changes in distribution of Rad51 during meiosis: (1) in early leptotene nuclei there are multiple, apparently randomly distributed, foci that by late leptonema become organized into tracks of foci. (2) These foci persist into zygonema, but most foci are now localized on Rad51-positive axes that correspond to lateral elements of the synaptonemal complex. As homologs synapse foci from homologous axes fuse. The distribution and involvement of Rad51 foci as contact points between homologs suggest that they may be components to early recombination nodules. (3) As pachynema progresses the number of foci drops dramatically; the temporal occurrence (mice) and physical and numerical distribution of foci on axes (chickens) suggest that they may be a component of late recombination nodules. (4) In early pachynema there are numerous Rad51 foci on the single axis of the X (mouse spermatocytes) or the Z (chicken oocytes) chromosomes that neither pair, nor recombine. (5) In late pachynema in mouse spermatocytes, but not oocytes, the Rad51 signal is preferentially enhanced at both ends of all the bivalents. As bivalents in spermatocytes, but not oocytes, begin to desynapse at diplonema they are often held together at these Rad51-positive termini. These observations parallel observations that recombination rates are exceptionally high near chromosome ends in male but not female eutherian mammals. (6) From diakinesis through metaphase I, Rad51 protein is detected as low-intensity fluorescent doublets that localize with CREST-specific antigens (kinetochores), suggesting that Rad51 participates, at least as a structural component of the materials involved, in sister kinetochore cohesiveness. Finally, the changes in Rad51 distribution during meiosis do not appear to be species specific, but intrinsic to the meiotic process.

Antagonistic interactions of an arsenic-containing mixture in a multiple organ carcinogenicity bioassay.

PubMed

Pott, W A; Benjamin, S A; Yang, R S

1998-11-27

Inorganic arsenic (As), 1,2-dichloroethane (DCE), vinyl chloride (VC) and trichloroethylene (TCE) are frequently identified as groundwater contaminants near hazardous waste disposal sites. While the carcinogenicity of each of these chemicals has been extensively studied individually, little information exists regarding their carcinogenic potential in combination. Therefore, we investigated the carcinogenic promoting potential of chemical mixtures containing arsenic, DCE, VC and TCE following multiple initiator administration in a multiple organ carcinogenicity bioassay (N. Ito, T. Shirai, S. Fukushima, Medium-term bioassay for carcinogens using multiorgan models, in: N. Ito, H. Sugano (Eds.), Modification of Tumor Development in Rodents, Prog. Exp. Tumor Res., 33, 41-57, Basel, Karger, 1991). Our results reveal a dose-responsive antagonistic effect of this four-chemical mixture on the development of preneoplastic hepatic lesions (altered hepatocellular foci and glutathione S-transferase pi positive foci) as well as bronchioalveolar hyperplasia and adenoma formation.

Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in mice.

PubMed

Serikov, Vladimir B; Mikhaylov, Viatcheslav M; Krasnodembskay, Anna D; Matthay, Michael A

2008-01-01

Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD(50) intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP(+) leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP(+) CD45(+) cells, GFP(+) vimentin-positive cells, and GFP(+) collagen I-positive fibroblasts. GFP(+) endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.

Extensive limb lengthening in Ollier's disease: 25-year follow-up.

PubMed

Märtson, Aare; Haviko, Tiit; Kirjanen, Kaur

2005-01-01

A case of extensive lower limb lengthening (32 cm) in a 14-year-old male patient with Ollier's disease is reported. A varus deformity of the femur and a valgus deformity of the tibia were evident. The femur was successfully lengthened 22 cm by metaphyseal distraction, and the tibia was lengthened 10 cm by two-stage distraction-compression method with a cylindrical bone allograft. Ilizarov's distraction device was used. Radiologically, a good bone regenerate was formed. Host bone has incorporated (like sarcophagi) the allograft of tibia. No evidence of vascular or neural disturbances was found. The lengthening indices were counted for femur 22.5 days per centimeter and for tibia 21 days per centimeter, altogether 15.5 days per centimeter. Bone lengthening was performed through the Ollier's disease foci. Fine needle biopsy investigation showed that most embryonic cartilage cells had been replaced with bone tissue. After five years and a 25-year follow-up the patient was satisfied with the result. The function of the knee joint was limited, but the limb was fully weight-bearing. Signs of knee osteoarthritis were found.

Characterization of Foci and Breakthrough Sites During Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: Studies Using High-Density (510-512 Electrodes) Biatrial Epicardial Mapping.

PubMed

Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Markowitz, Alan; Waldo, Albert L

2017-03-17

We previously demonstrated that persistent and long-standing persistent atrial fibrillation is maintained by activation emanating from foci and breakthrough sites of different cycle lengths (CLs). The purpose of this study was to characterize the behavior of focal and nonrandom breakthrough activation identified during high-density mapping of atrial fibrillation in these patients. During open heart surgery, we recorded activation from both atria simultaneously using 510 to 512 epicardial electrodes along with ECG lead II in 12 patients with persistent and long-standing persistent atrial fibrillation. For each patient, analysis of 32 consecutive seconds of activation from identified focal (sustained and/or intermittent) and nonrandom breakthrough sites was performed. Multiple foci (sustained and/or intermittent) of different CLs were present in both atria in 11 of 12 patients; 8 foci were sustained, and 22 were intermittent. Temporal CL behavior of sustained foci varied over time (≤20 ms of the mean CL). For intermittent foci, no activation periods were due to a spontaneous pause (18 of 22) or activation of the focus by another wave front (11 of 22). All patients had breakthrough activation. Seven patients had 12 nonrandom breakthrough sites. Periods of no breakthrough activation were caused by a spontaneous pause (6 of 12 patients) or activation from another wave front (4 of 12) or were uncertain (5 of 12). Focal and nonrandom breakthrough activation sometimes produced repetitive "wannabe" (incomplete) reentry in 6 of 12 patients. During persistent and long-standing persistent atrial fibrillation, sustained foci manifested variable CLs. Spontaneous pauses or activation from other wave fronts explained the intermittency of foci and nonrandom breakthrough. Focal and nonrandom breakthrough activation occasionally produced wannabe reentry. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Malignant adenomyoepithelioma of breast masquerading as soft tissue lytic lesion of right iliac bone: a rare entity.

PubMed

R, Kalyani; Murthy V, Srinivas

2014-09-01

Adenomyoepithelioma (AME) of breast is a low grade malignant biphasic tumour, usually seen in elderly women as a firm, well circumscribed tumour having both glandular and myoepithelial cells. The cells may show atypical features. The tumour may harbour foci of carcinoma which may be epithelial type, myoepithelial type, both or of metaplastic cells. The behaviour is hard to predict as it can be treated by local excision, recurrence is known or it can present with distant metastasis and hence the prognosis. We present a case of 50-year-old women who presented with right iliac bone lytic lesion diagnosed as metastatic deposits. Past history revealed that patient was diagnosed and treated for AME of right breast seven years back. The metastatic deposits also showed features of adenomyoepithelioma. Hence, a diagnosis of malignant AME deposits in right iliac bone was made.

Synaptic control of local translation: the plot thickens with new characters.

PubMed

Thomas, María Gabriela; Pascual, Malena Lucía; Maschi, Darío; Luchelli, Luciana; Boccaccio, Graciela Lidia

2014-06-01

The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

‘Tumour-induced osteomalacia’

PubMed Central

Munoz, Javier; Michel Ortega, Rosa; Celzo, Florence; Donthireddy, Vijayalakshmi

2012-01-01

A 60-year-old man presented 2 years before his diagnosis with long-standing muscle cramping, progressive generalised weakness and chronic hip pain. The patient was found to have bilateral femoral neck pathologic fractures therefore, underwent reamed intramedullary nailing of both femurs. Laboratory studies showed hypophosphataemia. Bone marrow biopsy was negative for malignancy. Positron emission tomography demonstrated fludeoxyglucose uptake only in the posterior neck. Bone scan showed innumerable foci of increased activity throughout the skeleton consistent with pseudofractures seen in osteomalacia. Fine needle aspiration from the mass in the neck revealed a phosphaturic mesenchymal tumour of mixed connective tissue type. Resection of the mass in the neck resulted in resolution of generalised complaints with no evidence of recurrence with a follow-up of 12 months. PMID:22736784

Learning with Multiple Representations: Infographics as Cognitive Tools for Authentic Learning in Science Literacy

ERIC Educational Resources Information Center

Gebre, Engida

2018-01-01

This paper presents a descriptive case study where infographics--visual representation of data and ideas--have been used as cognitive tools to facilitate learning with multiple representations in the context of secondary school students' science news reporting. Despite the complementary nature of the two research foci, studies on cognitive tools…

How We Manage Patients with Plasmacytomas.

PubMed

Fotiou, Despina; Dimopoulos, Meletios A; Kastritis, Efstathios

2018-04-17

To discuss the diagnostic approach, treatment options, and future considerations in the management of plasmacytomas, either solitary or in the context of overt multiple myeloma (MM). Advanced imaging techniques such as whole-body magnetic resonance imaging and positron emission tomography/computerized tomography are essential for the diagnostic workup of solitary plasmacytomas (SP) to rule out the presence of other disease foci. The role of flow cytometry and clonal plasma cell detection is currently under study together with other prognostic factors for the identification of patients with SP at high risk of progression to overt MM. Solitary plasmacytomas are treated effectively with local radiotherapy whereas systemic therapy is required at relapse. Clonal plasma cells that accumulate at extramedullary sites have distinct biological characteristics. Patients with MM and soft tissue involvement have poor outcomes and should be treated as ultra-high risk. A revised definition of SP that distinguishes between true solitary clonal PC accumulations and SP with minimal bone marrow involvement should be considered to guide an appropriate therapeutic and follow-up approach. Future studies should be conducted to determine optimum treatment approaches for patients with MM and paraskeletal or extramedullary disease.

Rare bone diseases and their dental, oral, and craniofacial manifestations.

PubMed

Foster, B L; Ramnitz, M S; Gafni, R I; Burke, A B; Boyce, A M; Lee, J S; Wright, J T; Akintoye, S O; Somerman, M J; Collins, M T

2014-07-01

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. © International & American Associations for Dental Research.

Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

PubMed Central

Foster, B.L.; Ramnitz, M.S.; Gafni, R.I.; Burke, A.B.; Boyce, A.M.; Lee, J.S.; Wright, J.T.; Akintoye, S.O.; Somerman, M.J.; Collins, M.T.

2014-01-01

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. PMID:24700690

Identifying aggressive prostate cancer foci using a DNA methylation classifier.

PubMed

Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

2017-01-12

Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

Hemothorax associated with telangiectatic osteosarcoma in a dog.

PubMed

Mahaffey, E A; Greene, C E

1985-08-01

Hemothorax in a dog was attributed to bleeding from an intrathoracic mass attached to the sixth through the tenth ribs. The mass contained numerous cavernous, blood-filled spaces as well as bands of osteoid and occasional foci of osseous tissue. The diagnosis was telangiectatic osteosarcoma. Telangiectatic osteosarcoma is an uncommon variant of osteosarcoma. Cavernous, blood-filled spaces and paucity of bone are important histologic features. Metastasis was described in one of the seven telangiectatic osteosarcomas reported in dogs, and none was found in this case.

Topographic effects on dispersal patterns of Phytophthora cinnamomi at a stand scale in a Spanish heathland

PubMed Central

Acedo, Angel; Abad, Enrique

2018-01-01

Phytophthora cinnamomi is one of the most important plant pathogens in the world, causing root rot in more than a thousand plant species. This observational study was carried out on a P. cinnamomi infected heathland of Erica umbellata used as goat pasture. The patterns and shapes of disease foci and their distribution were described in a spatial and temporal context using an aerial photograph record. A set of topographic traits was selected on the basis of a disease dynamic hypothesis and their effects on observed spatial disease patterns were analyzed. Incipient infections situated in flat terrain expanded as compact circular front patterns with a low growth rate. On slopes, disease patches developed more rapidly down slope, forming parabolic shapes. The axis direction of the parabolas was highly correlated with terrain aspect, while the parabolic amplitude was associated with land curvature and slope. New secondary foci appeared over the years producing an accelerated increase of the affected surface. These new foci were observed in sites where disease density was higher or near sites more frequently visited by animals such as the stable or the forage crop. In contrast, a smaller number of disease foci occur in areas which animals are reluctant to visit, such as where they have a short range of vision. Our results suggest that 1) the growth of existing P. cinnamomi foci is controlled by a combination of root-to-root contact and water flows, 2) the increase in the diseased area arises mainly from the multiplication of patches, 3) the formation of new foci is mediated by long-distance transport due to the movement of animals and humans along certain preferential pathways, and 4) geomorphology and topography traits are associated with the epidemiology of this soil-borne pathogen. PMID:29601576

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

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

Bao, B. C.; Wang, N.; Xu, Q.

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 exponentmore » 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.« less

21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Single/multiple component metallic bone fixation....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

Sarcocystosis in a stillborn lamb

USDA-ARS?s Scientific Manuscript database

Confirmed congenital sarcocystosis has not been reported in sheep and extremely rarely in other domestic ruminants. Sarcocystosis was diagnosed in a stillborn lamb with microscopic lesions predominantly in the central nervous system and placenta. Encephalitis was characterized by multiple foci of gl...

Carborundum, a bulk similar to dietary fibers but chemically inert, does not decrease colon carcinogenesis.

PubMed

Corpet, D E; Taché, S; Peiffer, G

1997-03-19

Dietary fibers might lower the risk of colorectal cancer, maybe because of their bulking effect. We tested the protection afforded by an inert bulk against carcinogenesis. Thirty rats received an azoxymethane injection and were allocated to a control diet, or to a diet supplemented with 10% carborundum. After 100 days the colons were scored for aberrant crypt foci. Compared to controls, the fecal weight was doubled in carborundum-fed rats (P < 0.001), but the aberrant crypt foci multiplicity was not changed (P = 0.92). The results do not support the hypothesis that intestinal dilution by an inert bulk can protect against colon cancer.

Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.

PubMed

Xu, Rongyao; Fu, Zongyun; Liu, Xue; Xiao, Tao; Zhang, Ping; Du, Yifei; Yuan, Hua; Cheng, Jie; Jiang, Hongbing

2016-11-01

Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of hepatocellular adenoma: Solitary-uncomplicated, multiple and ruptured tumors

PubMed Central

Toso, Christian; Majno, Pietro; Andres, Axel; Rubbia-Brandt, Laura; Berney, Thierry; Buhler, Léo; Morel, Philippe; Mentha, Gilles

2005-01-01

AIM: While hepatocellular adenomas (HAs) have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. METHODS: Twenty-five consecutive patients operated for solitary-uncomplicated (9), multiple (6), and ruptured (10) HAs were reviewed according to management strategies and outcomes. RESULTS: All solitary-uncomplicated HAs (ranged 2.2-14 cm in size) were removed. Out of 25 HAs, 2 (8%) included foci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA (ranged 1.7-10 cm in size) were initially managed with hemodynamic support and angiography, allowing the embolization of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d (range 4-70 d) after admission. CONCLUSION: Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery. PMID:16237767

[Severe infections in children with sickle cell disease: clinical aspects and prevention].

PubMed

Bégué, P; Castello-Herbreteau, B

2001-09-01

Sickle-cell disease (SCD) is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumonococcal bacteremia and meningitis due to S. pneumoniae are often lethal and justify the penicillin prophylaxis, which has provided a dramatic decrease in early mortality bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia, because they are often intricated. Osteomyelitis is generally due to Salmonella, most often S. enteritidis. Multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Osteomyelitis is less frequent in developed countries and must been differentiated with bone infarction by use of bone scintigraphy. Parvovirus B19 infection causes acute erythroblastopenias. Malaria does not result in cerebral malaria, but can lead to severe anaemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (osteomyelitis, meningitis), and M. pneumoniae (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at three months of age and no closely-spaced immunizations, most notably against peumococci, hepatitis B virus, S. typhi and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. New conjugated pneumococcal vaccines are effective in protecting very young infants and should therefore be used in sickle cell patients.

IMMUNOLOGIC MEMORY CELLS OF BONE MARROW ORIGIN

PubMed Central

Miller, Harold C.; Cudkowicz, Gustavo

1972-01-01

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F1 mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process. PMID:4553850

The protein PprI provides protection against radiation injury in human and mouse cells

PubMed Central

Shi, Yi; Wu, Wei; Qiao, Huiping; Yue, Ling; Ren, Lili; Zhang, Shuyu; Yang, Wei; Yang, Zhanshan

2016-01-01

Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c mouse cells with the yeast-derived PprI and elucidate the radioprotective effects the protein provides upon gamma irradiation. We see that PprI significantly increases the survival rate, antioxidant viability, and DNA-repair capacity in irradiated cells and decreases concomitant apoptosis rates and counts of damage-indicative γH2AX foci. Furthermore, we find that PprI reduces mortality and enhances bone marrow cell clone formation and white blood cell and platelet counts in irradiated mice. PprI also seems to alleviate pathological injuries to multiple organs and improve antioxidant viability in some tissues. Our results thus suggest that PprI has crucial radioprotective effects on irradiated human and mouse cells. PMID:27222438

Osteolipomatous metaplasia in the liver of cameloids

USGS Publications Warehouse

Stroud, R.K.; Griner, L.A.; Higgins, W.Y.

1982-01-01

An aged male Bactrian camel (Camelus ferus f. bactriana), originally from the San Diego Zoo, died suddenly. Necropsy showed acute bloat and chronic liver disease. In samples of liver tissue fixed in 10% neutral buffered formalin, approximately 25% of the total volume of tissue was comprised of multiple white to cream-colored circumscribed nodules up to 1 cm in diameter, which were gritty when cut (fig. 1).Samples of liver were cut at 6 μm for histologic examination. Microscopically, the nodules consisted of aggregations of large, vacuolated cells resembling fat cells with spicules of mature bone scattered throughout many nodules (fig. 2). Most nodules were circumscribed but not encapsulated. Single or small clusters of vacuolated cells, however, were scattered diffusely in the hepatic parenchyma surrounding the nodules. We found cholangitis and peribiliary fibrosis in some areas, but no generalized cirrhosis. Degeneration of hepatocytes was seen in some areas peripheral to the nodules. Compression of the hepatic architecture was evident in the liver parenchyma surrounding some nodules, but the primary change was infiltrative rather than expansive. Foci of lymphocytes and a few neutrophils were present in some nodules. Hematopoietic cells, described as a characteristic of myelolipomas, were not found in any of the nodules examined [2, 4].

Spontaneous Osteoblastic Osteosarcoma in a Mongolian Gerbil (Meriones unguiculatus)

PubMed Central

Salyards, Gregory W; Blas-Machado, Uriel; Mishra, Sasmita; Harvey, Stephen B; Butler, Abigail M

2013-01-01

Spontaneous neoplasms in Mongolian gerbils have an incidence of 20% to 26.8%, but osteosarcomas occur at a much lower rate. Here we report a 1-y-old Mongolian gerbil with a spontaneous osteosarcoma at the level of the proximal tibia, with metastases to the pectoral muscles and lungs. Grossly, the tibial mass obliterated the tibia and adjacent muscles, and an axillary mass with a bloody, cavitary center expanded the pectoral muscles. Microscopically, the tibial mass was an infiltrative, osteoblastic mesenchymal neoplasm, and the axillary mass was an anaplastic mesenchymal neoplasm with hemorrhage. The lung contained multiple metastatic foci. Immunohistochemistry for osteonectin was strongly positive in the tibial, axillary, and pulmonary metastases. Although osteosarcoma is the most common primary malignant bone neoplasm that occurs spontaneously in all laboratory and domestic animal species and humans, it arises less frequently than does other neoplasms. The current case of spontaneous osteoblastic osteosarcoma of the proximal tibia and metastases to the pectoral muscles and lung in a Mongolian gerbil is similar in presentation, histology, and predilection site of both osteoblastic and telangiectatic osteosarcomas in humans. In addition, this case is an unusual manifestation of osteosarcoma in the appendicular skeleton of a Mongolian gerbil. PMID:23561939

Extrachromosomal Nucleolus-Like Compartmentalization by a Plasmid-Borne Ribosomal RNA Operon and Its Role in Nucleoid Compaction.

PubMed

Mata Martin, Carmen; Sun, Zhe; Zhou, Yan Ning; Jin, Ding Jun

2018-01-01

In the fast-growing Escherichia coli cells, RNA polymerase (RNAP) molecules are concentrated and form foci at clusters of ribosomal RNA (rRNA) operons resembling eukaryotic nucleolus. The bacterial nucleolus-like organization, spatially compartmentalized at the surface of the compact bacterial chromosome (nucleoid), serves as transcription factories for rRNA synthesis and ribosome biogenesis, which influences the organization of the nucleoid. Unlike wild type that has seven rRNA operons in the genome in a mutant that has six (Δ6 rrn ) rRNA operons deleted in the genome, there are no apparent transcription foci and the nucleoid becomes uncompacted, indicating that formation of RNAP foci requires multiple copies of rRNA operons clustered in space and is critical for nucleoid compaction. It has not been determined, however, whether a multicopy plasmid-borne rRNA operon (p rrnB ) could substitute the multiple chromosomal rRNA operons for the organization of the bacterial nucleolus-like structure in the mutants of Δ6 rrn and Δ7 rrn that has all seven rRNA operons deleted in the genome. We hypothesized that extrachromosomal nucleolus-like structures are similarly organized and functional in trans from p rrnB in these mutants. In this report, using multicolor images of three-dimensional superresolution Structured Illumination Microscopy (3D-SIM), we determined the distributions of both RNAP and NusB that are a transcription factor involved in rRNA synthesis and ribosome biogenesis, p rrnB clustering, and nucleoid structure in these two mutants in response to environmental cues. Our results found that the extrachromosomal nucleolus-like organization tends to be spatially located at the poles of the mutant cells. In addition, formation of RNAP foci at the extrachromosomal nucleolus-like structure condenses the nucleoid, supporting the idea that active transcription at the nucleolus-like organization is a driving force in nucleoid compaction.

Modelling dengue epidemic spreading with human mobility

NASA Astrophysics Data System (ADS)

Barmak, D. H.; Dorso, C. O.; Otero, M.

2016-04-01

We explored the effect of human mobility on the spatio-temporal dynamics of Dengue with a stochastic model that takes into account the epidemiological dynamics of the infected mosquitoes and humans, with different mobility patterns of the human population. We observed that human mobility strongly affects the spread of infection by increasing the final size and by changing the morphology of the epidemic outbreaks. When the spreading of the disease is driven only by mosquito dispersal (flight), a main central focus expands diffusively. On the contrary, when human mobility is taken into account, multiple foci appear throughout the evolution of the outbreaks. These secondary foci generated throughout the outbreaks could be of little importance according to their mass or size compared with the largest main focus. However, the coalescence of these foci with the main one generates an effect, through which the latter develops a size greater than the one obtained in the case driven only by mosquito dispersal. This increase in growth rate due to human mobility and the coalescence of the foci are particularly relevant in temperate cities such as the city of Buenos Aires, since they give more possibilities to the outbreak to grow before the arrival of the low-temperature season. The findings of this work indicate that human mobility could be the main driving force in the dynamics of vector epidemics.

Evaluation of cholesteatoma: our experience with DW Propeller imaging.

PubMed

Karandikar, Amit; Loke, Siu Cheng; Goh, Julian; Yeo, Seng Beng; Tan, Tiong Yong

2015-09-01

Cholesteatoma management includes early detection and surgical exploration. Due to its tendency to recur, it can be potentially locally aggressive. Magnetic resonance imaging (MRI), and in particular diffusion weighted imaging (DWI), plays an important role in management of these lesions. To assess the accuracy of Propeller (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) DW sequence in detecting middle ear and mastoid cholesteatomas in non-operated ears by surgical correlation. A retrospective review of 15 patients was done who underwent Propeller DWI with either clinically confirmed or suspected cholesteatomas. Surgical correlation was done in all cases. All patients had hyperintense foci on Propeller DWI. Surgical correlation performed revealed that 13 patients had cholesteatomas while two patients had mastoid abscesses. The location, extent, and size of cholesteatomas on Propeller DWI matched with the operative findings. Of the 13 patients with cholesteatomas, three patients had multiple foci of hyperintensity on Propeller DWI, which corroborated with the surgical finding of multiple cholesteatomas. The average apparent diffusion coefficient value of cholesteatoma was 0.868 × 10(-3) mm(2)/s, found to be higher than that of abscess, which was 0.425 × 10(-3) mm(2)/s. Propeller DWI was accurate in assessing the location, extent, and size of cholesteatomas as corroborated with surgical findings. Propeller DWI is useful in detecting number of cholesteatoma foci, a vital finding as it may impact the choice of surgery. © The Foundation Acta Radiologica 2014.

Naming the body (or the bones): Human remains, anthropological/medical collections, religious beliefs, and restitution.

PubMed

Charlier, Philippe

2014-04-01

Human bones and biological remains conserved in anthropological, medical, and archaeological collections are foci of ethical debate, as recently illustrated by the affair of Charles Byrne's bones. In the near future, curators will have to choose between global conservation of all (or almost all) anthropological collections and systematic restitution to their original communities or families. Various proposals and examples of restitution and nonrestitution are given (with justifications) in order to support the concept that the body (especially the dead body) is not property. We propose that the only element supporting arguments in favor of restitution could be the name of the individual, highlighting the importance of all identification processes for such "artifacts." This is undoubtedly a universal value: naming the dead, identifying and then burying the person, i.e., reversing the progression along the timeline from individual to scientific specimen. Such elements could be of great interest to all universities and medical institutions that keep human remains in their collections for educational or historical purposes when they are confronted with ethical problems and/or repatriation requests. Copyright © 2014 Wiley Periodicals, Inc.

Bone marrow invasion in multiple myeloma and metastatic disease.

PubMed

Vilanova, J C; Luna, A

2016-04-01

Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Histiocytic Sarcoma and Bilateral Facial Vein Thrombosis in a Siberian Hamster (Phodopus sungorus).

PubMed

Coble, Dondrae J; Shoemaker, Margaret; Harrington, Bonnie; Dardenne, Adrienne D; Bolon, Brad

2015-04-01

A 21-mo-old, male Siberian hamster (Phodopus sungorus) presented with left-sided facial swelling, proptosis of the left eye, and blepharospasm of the right eye. The hamster had been used only for breeding. Because of the poor prognosis, the hamster was euthanized without additional diagnostic assays or treatments. Routine gross pathologic evaluation demonstrated exophthalmos and presumptive hyphema of the left eye, bilateral facial edema, freely movable nodules within the mesentery, white foci within the liver, and a large mass effacing the cranial pole of the right kidney. On histologic evaluation, the mesenteric nodules and liver foci expressed histiocytic marker CD163 and thus were diagnosed as sites of histiocytic sarcoma, whereas the kidney mass was a well-differentiated renal cell carcinoma. The facial swelling resulted from bilateral, chronic, severe, branching thrombi in many facial veins. Additional age-related histopathologic findings were observed in other organs, including diffuse glomerulopathy, nesidioblastosis (pancreatic islet neoformation), and multiple foci of severe cartilage degeneration in the axial skeleton. To our knowledge, this report provides the first description of histiocytic sarcoma in a Siberian hamster.

Systemic phaeohyphomycosis caused by Xylohypha bantiana in a dog.

PubMed

Schroeder, H; Jardine, J E; Davis, V

1994-12-01

An 8-year-old, Maltese-cross bitch presented with chronic neck and back pain and an acute onset of circling, hyperaesthesia and constant crying. Clinical examination revealed temporal muscle atrophy, an abnormal hanging reflex, cervical rigidity and severe hepatomegaly. Ultrasonography of the liver showed several disseminated, poorly demarcated, hypoechoic areas which on fine needle aspirates, contained large numbers of pigmented fungal hyphae. Cerebrospinal fluid examination revealed fungal hyphae and numerous Ehrlichia canis morulae. A diagnosis of systemic phaeohyphomycosis secondary to ehrlichiosis was proposed. Treatment was unsuccessful and the dog was euthanased. At necropsy, multiple yellowish-green to black, necro-granulomatous foci were found throughout the liver parenchyma and similar foci were present in the spleen, renal cortices and adrenal glands. Irregular, multifocal, grey to black foci of malacia were present in both the grey and the white matter of the brain. On histopathological examination pigmented fungal hyphae were demonstrated in the liver, spleen, kidneys, portal lymph node and adrenals, as well as in the brain. Cultures of various organs yielded a fungal organism identified as Xylohypha bantiana.

Physical Environments of Assisted Living: Research Needs and Challenges

ERIC Educational Resources Information Center

Cutler, Lois J.

2007-01-01

Purpose: This article aims to review research measures and findings related to physical environments of assisted living (AL) according to multiple conceptual perspectives--ecological, cultural, and Maslovian hierarchy. Design and Methods: A literature and research review was undertaken with two foci: performance measures for physical environments,…

PKCε Is an Essential Mediator of Prostate Cancer Bone Metastasis.

PubMed

Gutierrez-Uzquiza, Alvaro; Lopez-Haber, Cynthia; Jernigan, Danielle L; Fatatis, Alessandro; Kazanietz, Marcelo G

2015-09-01

The bone is a preferred site for metastatic homing of prostate cancer cells. Once prostate cancer patients develop skeletal metastases, they eventually succumb to the disease; therefore, it is imperative to identify key molecular drivers of this process. This study examines the involvement of protein kinase C epsilon (PKCε), an oncogenic protein that is abnormally overexpressed in human tumor specimens and cell lines, on prostate cancer cell bone metastasis. PC3-ML cells, a highly invasive prostate cancer PC3 derivative with bone metastatic colonization properties, failed to induce skeletal metastatic foci upon inoculation into nude mice when PKCε expression was silenced using shRNA. Interestingly, while PKCε depletion had only marginal effects on the proliferative, adhesive, and migratory capacities of PC3-ML cells in vitro or in the growth of xenografts upon s.c. inoculation, it caused a significant reduction in cell invasiveness. Notably, PKCε was required for transendothelial cell migration (TEM) as well as for the growth of PC3-ML cells in a bone biomimetic environment. At a mechanistic level, PKCε depletion abrogates the expression of IL1β, a cytokine implicated in skeletal metastasis. Taken together, PKCε is a key factor for driving the formation of bone metastasis by prostate cancer cells and is a potential therapeutic target for advanced stages of the disease. This study uncovers an important new function of PKCε in the dissemination of cancer cells to the bone; thus, highlighting the promising potential of this oncogenic kinase as a therapeutic target for skeletal metastasis. ©2015 American Association for Cancer Research.

Repair of calvarial bone defects in mice using electrospun polystyrene scaffolds combined with β-TCP or gold nanoparticles.

PubMed

Terranova, Lisa; Dragusin, Diana Maria; Mallet, Romain; Vasile, Eugeniu; Stancu, Izabela-Cristina; Behets, Catherine; Chappard, Daniel

2017-02-01

Non-biodegradable porous polystyrene (PS) scaffolds, composed of microfibers, have been prepared by electrospinning for the reconstruction of large bone defects. PS microfibers were prepared by incorporating β-TCP grains inside the polymer or grafting gold nanoparticles surface functionalized with mercaptosuccinic acid. Cytocompatibility of the three types of scaffolds (PS, β-TCP-PS and Au-PS) was studied by seeding human mesenchymal stem cells. Biocompatibility was evaluated by implanting β-TCP-PS and Au-PS scaffolds into a critical size (4mm) calvarial defect in mice. Calvaria were taken 6, 9, and 12 weeks after implantation; newly formed bone and cellular response was analyzed by microcomputed tomography (microCT) and histology. β-TCP-PS scaffolds showed a significantly higher cell proliferation in vitro than on PS or Au-PS alone; clearly, the presence of β-TCP grains improved cytocompatibility. Biocompatibility study in the mouse calvaria model showed that β-TCP-PS scaffolds were significantly associated with more newly-formed bone than Au-PS. Bone developed by osteoconduction from the defect margins to the center. A dense fibrous connective tissue containing blood vessels was identified histologically in both types of scaffolds. There was no inflammatory foci nor giant cell in these areas. AuNPs aggregates were identified histologically in the fibrosis and also incorporated in the newly-formed bone matrix. Although the different types of PS microfibers appeared cytocompatible during the in vitro experiment, they appeared biotolerated in vivo since they induced a fibrotic reaction associated with newly formed bone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis

PubMed Central

Georgescu, Walter; Osseiran, Alma; Rojec, Maria; Liu, Yueyong; Bombrun, Maxime; Tang, Jonathan; Costes, Sylvain V.

2015-01-01

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation. PMID:26107175

Characterizing the DNA damage response by cell tracking algorithms and cell features classification using high-content time-lapse analysis

DOE PAGES

Georgescu, Walter; Osseiran, Alma; Rojec, Maria; ...

2015-06-24

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were ablemore » to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm 2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Furthermore, such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.« less

Secondary sea-blue histiocytosis derived from Niemann-Pick disease.

PubMed

Suzuki, Osamu; Abe, Masafumi

2007-04-01

Sea-blue histiocytosis is a rare disorder seen in patients with lipid metabolic or ceroid storage diseases. Sea-blue histiocytes are ceroid-laden macrophages detectable by May-Giemsa staining. We report a case of a 28-year-old woman diagnosed with Niemann-Pick disease at 2 or 3 years of age. To confirm this diagnosis, we examined her bone marrow, which revealed scattered foci containing aggregates of foamy macrophages. May-Giemsa staining identified blue-staining foamy macrophages, referred to as sea-blue histiocytes. In summary, we report the detection of sea-blue histiocytosis in an adult with Niemann-Pick disease.

Associated aneurysmal bone cyst and cemento-osseous dysplasia: a case report and review of the literature.

PubMed

Jacomacci, Willian Pecin; Veloso Perdigão, João Paulo; Veltrini, Vanessa Cristina; Farah, Gustavo Jacobucci; Tolentino, Elen Souza; Vessoni Iwaki, Lilian Cristina; Iwaki Filho, Liogi

2017-01-01

The purpose of this case report is to describe a previously unpublished association between focal cemento-osseous dysplasia (FCOD) and an aneurysmal bone cyst (ABC) and review the literature with regard to associated benign fibro-osseous lesions and cysts. A 41-year-old woman without a history of trauma presented with asymptomatic swelling in the right side of the mandible. Radiographs of the region revealed a unilocular radiolucent area with radiopaque foci. After aspiration of the lesion was positive for serosanguineous fluid, complete excision of the lesion was performed. Microscopic examination revealed a hybrid ABC and FCOD. The 12-month follow-up showed significant bone repair and no signs of recurrence. A review of the English-language literature from 1980 to 2012 revealed 1 retrospective study, 4 case series, and 18 single-case reports on the topic of cemento-osseous dysplasias, fibro-osseous lesions, and aneurysmal bone cysts. Of 59 cases, none reported an association between an ABC and FCOD. Although fibro-osseous lesions do not require intervention, surgical excision is recommended when they are associated with cysts. This case, in which an ABC and FCOD were associated, reinforces the need for a careful diagnostic process in radiographically mixed lesions that respond positively to aspiration biopsy.

Synthetic Bone Substitute Engineered with Amniotic Epithelial Cells Enhances Bone Regeneration after Maxillary Sinus Augmentation

PubMed Central

Barboni, Barbara; Mangano, Carlo; Valbonetti, Luca; Marruchella, Giuseppe; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mauro, Annunziata; Bedini, Rossella; Turriani, Maura; Pecci, Raffaella; Nardinocchi, Delia; Zizzari, Vincenzo Luca; Tetè, Stefano; Piattelli, Adriano; Mattioli, Mauro

2013-01-01

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 cm3), alone or engineered with 1×106 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 ability to switch-on the expression of a specific bone-related protein (osteocalcin, OCN) when transplanted into host tissues. PMID:23696804

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

PubMed Central

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-01-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

A decade review of publications in Families, Systems, & Health: 2005-2015.

PubMed

Mendenhall, Tai J; Li, Yiting; Schulz, Catherine L

2016-09-01

The purpose of this investigation was to review recent publication content and trends in Families, Systems, & Health ( FSH ). How do the journal’s articles reflect current and emerging challenges in health care? We hope that our findings can guide special issues and content foci. All work published in FSH between 2005 and 2015 was included (n = 452); each piece was coded for article type, general foci, and specific foci. The most common type of article published over the 10-year time frame was research reports (43%; n = 195), followed by other types (e.g., tribute pieces, poems), commentaries, conceptual/theory papers, literature reviews, and case studies. The most common general focus included family health and/or functioning (28%; n = 128). The most common specific foci centered on children (15%; n = 55). Common themes found in FSH ’s most frequently cited publications included family relationships in care, chronic physical illnesses, and mental health. Marked trends in journal content included increases in articles targeting family health and/or functioning and primary care and decreased attention to theory. FSH’s emphasis on research reports to inform current and evolving interventions that target contemporary health challenges suggests that the journal is keeping stride with the most pressing issues in health care today. Future special issues can continue to serve and meet these needs. FSH’s robust inclusion of other article types sustains the journal’s mission to advance multiple ways of understanding health-care phenomena. PsycINFO Database Record (c) 2016 APA, all rights reserved

Nonword Repetition, Phonological Storage, and Multiple Determinations

ERIC Educational Resources Information Center

Gupta, Prahlad

2006-01-01

The proposals that (a) nonword repetition and word learning both rely on phonological storage and (b) both are multiply determined are two of the major foci of Gathercole's (2006) Keynote Article, which marshals considerable evidence in support of each. In my view, the importance of these proposals cannot be overstated: these two notions go to the…

Visualising large hierarchies with Flextree

NASA Astrophysics Data System (ADS)

Song, Hongzhi; Curran, Edwin P.; Sterritt, Roy

2003-05-01

One of the main tasks in Information Visualisation research is creating visual tools to facilitate human understanding of large and complex information spaces. Hierarchies, being a good mechanism in organising such information, are ubiquitous. Although much research effort has been spent on finding useful representations for hierarchies, visualising large hierarchies is still a difficult topic. One of the difficulties is how to show both tructure and node content information in one view. Another is how to achieve multiple foci in a focus+context visualisation. This paper describes a novel hierarchy visualisation technique called FlexTree to address these problems. It contains some important features that have not been exploited so far. In this visualisation, a profile or contour unique to the hierarchy being visualised can be gained in a histogram-like layout. A normalised view of a common attribute of all nodes can be acquired, and selection of this attribute is controllable by the user. Multiple foci are consistently accessible within a global context through interaction. Furthermore it can handle a large hierarchy that contains several thousand nodes in a PC environment. In addition results from an informal evaluation are also presented.

Distinguishing rhinitis and nasal neoplasia by radiography.

PubMed

Russo, M; Lamb, C R; Jakovljevic, S

2000-01-01

To compare the incidence of radiographic signs in dogs with rhinitis and primary nasal neoplasia and to assess the performance of observers for distinguishing these conditions, the nasal radiographs of 72 dogs with either rhinitis (n = 42) or primary nasal neoplasia (n = 30) were examined by two independent observers using custom-designed forms to record their interpretations. Rhinitis was associated with a higher incidence of focal or multifocal lesions, localised soft tissue opacities, lucent foci, and a lack of frontal sinus involvement. Neoplasia was associated with soft tissue opacities and loss of turbinate detail that affected the entire ipsilateral nasal cavity, signs of invasion of the bones surrounding the nasal cavity, and soft tissue/fluid opacities within the ipsilateral frontal sinus. The signs with the highest positive predictive value (PPV) for rhinitis were absence of frontal sinus lesions and lucent foci in nasal cavity (PPV of each 82%), and invasion of surrounding bones for neoplasia (PPV 88%). There were no significant differences in the position of the lesion within the nasal cavity, incidence of unilateral versus bilateral lesions, calcified lesions, or absence of teeth. There was moderate agreement between observers about the diagnosis (kappa 0.59). Areas (SE) under ROC curves were 0.94 (0.03) and 0.96 (0.03) for observers A and B, respectively (not significantly different; P = 0.68). These results indicate a high accuracy for radiologists examining dogs with nasal diseases. Differentiation of rhinitis and nasal neoplasia should be based on finding combinations of radiologic signs that together have a high PPV. Differences in interpretation between experienced observers in this study suggest that certain signs are potential sources of error.

Maternal embryonic leucine zipper kinase inhibitor OTSSP167 has preclinical activity on multiple myeloma bone disease.

PubMed

Muller, Joséphine; Bolomsky, Arnold; Dubois, Sophie; Duray, Elodie; Stangelberger, Kathrin; Plougonven, Erwan; Lejeune, Margaux; Léonard, Angélique; Marty, Caroline; Hempel, Ute; Baron, Frédéric; Beguin, Yves; Cohen-Solal, Martine; Ludwig, Heinz; Heusschen, Roy; Caers, Jo

2018-05-10

Multiple myeloma bone disease is characterized by an uncoupling of bone remodeling in the multiple myeloma microenvironment, resulting in the development of lytic bone lesions. Most myeloma patients suffer from these bone lesions, which not only causes morbidity but also negatively impacts survival. The development of novel therapies, ideally with a combined anti-resorptive and bone-anabolic effect, is of great interest because lesions persist with the current standard of care, even in patients in complete remission. We have previously shown that MELK plays a central role in proliferation-associated high-risk multiple myeloma and its inhibition with OTSSP167 resulted in decreased tumor load. MELK inhibition in bone cells has not yet been explored, although some reports suggest factors downstream of MELK stimulate osteoclast activity and inhibit osteoblast activity, which makes MELK inhibition a promising therapeutic approach. Therefore, we assessed the effect of OTSSP167 on bone cell activity and the development of myeloma-induced bone disease. OTSSP167 inhibited osteoclast activity in vitro by decreasing progenitor viability as well as via a direct anti-resorptive effect on mature osteoclasts. In addition, OTSSP167 stimulated matrix deposition and mineralization by osteoblasts in vitro. This combined anti-resorptive and osteoblast-stimulating effect of OTSSP167 resulted in the complete prevention of lytic lesions and bone loss in myeloma-bearing mice. Immunohistomorphometric analyses corroborated our in vitro findings. In conclusion, we show that OTSSP167 has a direct effect on myeloma-induced bone disease in addition to its anti-multiple myeloma effect, which warrants further clinical development of MELK inhibition in multiple myeloma. Copyright © 2018, Ferrata Storti Foundation.

Method of reduction of the number of driving system channels for phased-array transducers using isolation transformers.

PubMed

Fjield, T; Hynynen, K

2000-01-01

Phased-array technology offers an incredible advantage to therapeutic ultrasound due to the ability to electronically steer foci, create multiple foci, or to create an enlarged focal region by using phase cancellation. However, to take advantage of this flexibility, the phased-arrays generally consist of many elements. Each of these elements requires its own radio-frequency generator with independent amplitude and phase control, resulting in a large, complex, and expensive driving system. A method is presented here where in certain cases the number of amplifier channels can be reduced to a fraction of the number of transducer elements, thereby simplifying the driving system and reducing the overall system complexity and cost, by using isolation transformers to produce 180 degrees phase shifts.

Multifocal fibrosing thyroiditis: report of 55 cases of a poorly recognized entity.

PubMed

Fellegara, Giovanni; Rosai, Juan

2015-03-01

During the course of our consultation activity, we have recognized a peculiar form of thyroiditis in which multiple foci of fibrosis, most of which were associated with reactive atypia of the surrounding follicles, are present. We have referred to this condition, both in our consultation reports and in the third series of A.F.I.P. Fascicle on Tumors of the Thyroid Gland, as "multifocal fibrosing thyroiditis" or (less frequently) "multifocal sclerosing thyroiditis," which are descriptive terms that highlight the benign/inflammatory nature of the process, its multiplicity, and its unknown pathogenesis. The aim of this study is to better define the morphologic features of this process and correlate it with some clinical data. With this purpose, the consultation files of one of the authors (J.R.) were searched for cases coded as multifocal fibrosing thyroiditis or multifocal sclerosing thyroiditis in a 20-year period ranging from January 1989 to December 2009. A total of 55 cases were identified that displayed the above-listed features. There were 51 (93%) female and 4 (7%) male patients (F/M=12.75), with ages ranging between 15 and 71 years (mean age, 47.03 y; median age, 44.5 y). Microscopically, multiple foci of fibrosis were identified in all cases, their number ranging from 2 to 51 per case (mean number, 16), with a mean diameter of 3 mm (range: 0.36 to 15.1 mm). Although heterogenous in shape and size, the individual foci were rather similar to each other in composition, being characterized by a fibrotic poorly cellular center that merged with a cellular peripheral zone. Some of the follicular structures present at the periphery of the scar and-to a lesser extent-those entrapped inside it underwent complex reactive and regenerative (atypical) changes that simulated malignancy. We discuss the differential diagnosis with other benign and malignant thyroid conditions and speculate about its pathogenesis and possible relationship with papillary thyroid microcarcinoma.

Magma Reservoirs Feeding Giant Radiating Dike Swarms: Insights from Venus

NASA Technical Reports Server (NTRS)

Grosfils, E. B.; Ernst, R. E.

2003-01-01

Evidence of lateral dike propagation from shallow magma reservoirs is quite common on the terrestrial planets, and examination of the giant radiating dike swarm population on Venus continues to provide new insight into the way these complex magmatic systems form and evolve. For example, it is becoming clear that many swarms are an amalgamation of multiple discrete phases of dike intrusion. This is not surprising in and of itself, as on Earth there is clear evidence that formation of both magma reservoirs and individual giant radiating dikes often involves periodic magma injection. Similarly, giant radiating swarms on Earth can contain temporally discrete subswarms defined on the basis of geometry, crosscutting relationships, and geochemical or paleomagnetic signatures. The Venus data are important, however, because erosion, sedimentation, plate tectonic disruption, etc. on Earth have destroyed most giant radiating dike swarm's source regions, and thus we remain uncertain about the geometry and temporal evolution of the magma sources from which the dikes are fed. Are the reservoirs which feed the dikes large or small, and what are the implications for how the dikes themselves form? Does each subswarm originate from a single, periodically reactivated reservoir, or do subswarms emerge from multiple discrete geographic foci? If the latter, are these discrete foci located at the margins of a single large magma body, or do multiple smaller reservoirs define the character of the magmatic center as a whole? Similarly, does the locus of magmatic activity change with time, or are all the foci active simultaneously? Careful study of giant radiating dike swarms on Venus is yielding the data necessary to address these questions and constrain future modeling efforts. Here, using giant radiating dike swarms from the Nemesis Tessera (V14) and Carson (V43) quadrangles as examples, we illustrate some of the dike swarm focal region diversity observed on Venus and briefly explore some key implications for the questions framed above.

Expression of nociceptive ligands in canine osteosarcoma.

PubMed

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Role of Bruton’s tyrosine kinase in myeloma cell migration and induction of bone disease

PubMed Central

Bam, Rakesh; Ling, Wen; Khan, Sharmin; Pennisi, Angela; Venkateshaiah, Sathisha Upparahalli; Li, Xin; van Rhee, Frits; Usmani, Saad; Barlogie, Bart; Shaughnessy, John; Epstein, Joshua; Yaccoby, Shmuel

2014-01-01

Myeloma cells typically grow in bone, recruit osteoclast precursors and induce their differentiation and activity in areas adjacent to tumor foci. Bruton’s tyrosine kinase (BTK), of the TEC family, is expressed in hematopoietic cells and is particularly involved in B-lymphocyte function and osteoclastogenesis. We demonstrated BTK expression in clinical myeloma plasma cells, interleukin (IL) –6– or stroma–dependent cell lines and osteoclasts. SDF-1 induced BTK activation in myeloma cells and BTK inhibition by small hairpin RNA or the small molecule inhibitor, LFM-A13, reduced their migration toward stromal cell-derived factor-1 (SDF-1). Pretreatment with LFM-A13 also reduced in vivo homing of myeloma cells to bone using bioluminescence imaging in the SCID-rab model. Enforced expression of BTK in myeloma cell line enhanced cell migration toward SDF-1 but had no effect on short-term growth. BTK expression was correlated with cell-surface CXCR4 expression in myeloma cells (n = 33, r = 0.81, P < 0.0001), and BTK gene and protein expression was more profound in cell-surface CXCR4-expressing myeloma cells. BTK was not upregulated by IL-6 while its inhibition had no effect on IL-6 signaling in myeloma cells. Human osteoclast precursors also expressed BTK and cell-surface CXCR4 and migrated toward SDF-1. LFM-A13 suppressed migration and differentiation of osteoclast precursors as well as bone-resorbing activity of mature osteoclasts. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibited osteoclast activity, prevented myeloma-induced bone resorption and moderately suppressed myeloma growth. These data demonstrate BTK and cell-surface CXCR4 association in myeloma cells and that BTK plays a role in myeloma cell homing to bone and myeloma-induced bone disease. PMID:23456977

Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant: 1-Day, 3-Week, and 3-Month Repair.

PubMed

Bell, Angela D; Lascau-Coman, Viorica; Sun, Jun; Chen, Gaoping; Lowerison, Mark W; Hurtig, Mark B; Hoemann, Caroline D

2013-04-01

Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects. In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro-computed tomography. Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12). Bone plate-induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant.

Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant

PubMed Central

Bell, Angela D.; Lascau-Coman, Viorica; Sun, Jun; Chen, Gaoping; Lowerison, Mark W.; Hurtig, Mark B.

2013-01-01

Objective: Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects. Design: In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro–computed tomography. Results: Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12). Conclusion: Bone plate–induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant. PMID:26069656

3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and osteogenesis.

PubMed

Min, Zhu; Shichang, Zhao; Chen, Xin; Yufang, Zhu; Changqing, Zhang

2015-08-01

Angiogenesis-osteogenesis coupling processes are vital in bone tissue engineering. Normal biomaterials implanted in bone defects have issues in the sufficient formation of blood vessels, especially in the central part. Single delivery of vascular endothelial growth factors (VEGF) to foci in previous studies did not show satisfactory results due to low loading doses, a short protein half-life and low efficiency. Development of a hypoxia-mimicking microenvironment for cells by local prolyl-4-hydroxylase inhibitor release, which can stabilize hypoxia-inducible factor 1α (HIF-1α) expression, is an alternative method. The aim of this study was to design a dimethyloxallyl glycine (DMOG) delivering scaffold composed of mesoporous bioactive glasses and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) polymers (MPHS scaffolds), so as to investigate whether the sustained release of DMOG promotes local angiogenesis and bone healing. The morphology and microstructure of composite scaffolds were characterized. The DMOG release patterns from scaffolds loaded with different DMOG dosages were evaluated, and the effects of DMOG delivery on human bone marrow stromal cell (hBMSC) adhesion, viability, proliferation, osteogenic differentiation and angiogenic-relative gene expressions with scaffolds were also investigated. In vivo studies were carried out to observe vascular formations and new bone ingrowth with DMOG-loaded scaffolds. The results showed that DMOG could be released in a sustained manner over 4 weeks from MPHS scaffolds and obviously enhance the angiogenesis and osteogenesis in the defects. Microfil perfusion showed a significantly increased formation of vessels in the defects with DMOG delivery. Furthermore, micro-CT imaging and fluorescence labeling indicated larger areas of bone formation for DMOG-loaded scaffolds. It is concluded that MPHS-DMOG scaffolds are promising for enhancing bone healing of osseous defects.

Healing process of vascular cutting edge using an Nd:YAG laser bipolar dissector.

PubMed

Morita, T; Ishida, K; Ookubo, K; Tanaka, K; Nakamura, H; Daikuzono, N

1995-08-01

The wound healing process was histopathologically investigated in a rabbit femoral artery (n = 48) after transection using a laser bipolar dissector (LBD, 1064nm the Nd:YAG bipolar contact laser) with laser power of 13W in 0.5-sec pulses. The cutting edges were harvested immediately (n = 6) and at 1 (n = 6), 4 (n = 6), and 7 (n = 6) days, 2 (n = 6), 3 (n = 6), and 4 (n = 6) weeks, and 6 months (n = 6), and evaluated by light microscopy. During the postoperative period, no perforation was seen in the 48 transected sites with the LBD. The healing process after LBD transection was accomplished within 2 weeks by organization of the intraluminal thrombus and by the formation of granulation tissue outside the adventitia of vessels. Characteristic morphological changes after LBD transection were recognized in the tapering area, i.e., cartilage and bone formation. Cartilaginous foci (n = 6) were observed in the media at 4 weeks after transection, and osseous foci (n = 3) in subendothelial space at 6 months. These observations may suggest that the heterotopic cartilaginous and osseous metaplasia of a vessel wall may be a result of the biostimulative effects of the Nd:YAG laser.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

PubMed

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular Testing in Multiple Synchronous Lung Adenocarcinomas: Case Report and Literature Review.

PubMed

Rafael, Oana C; Lazzaro, Richard; Hasanovic, Adnan

2016-02-01

Discovery of driver mutations in pulmonary adenocarcinoma has revolutionized the field of thoracic oncology with major impact on therapy and diagnosis. Testing for EGFR, ALK, and KRAS mutations has become part of everyday practice. We report a case with multiple synchronous primary pulmonary adenocarcinomas in a 72-year-old female with previous history of smoking. The patient presented with cough and bilateral lung ground glass opacities. A positron emission tomography/computed tomography scan showed no activity in mediastinal lymph nodes. She underwent a left upper lobe biopsy and a right upper lobe wedge resection. Pathology revealed 4 morphologically distinct adenocarcinoma foci, suggestive of synchronous primary lung tumors. Molecular testing demonstrated no mutation in the left tumor. Three different driver mutations were present in the right lung tumors: KRAS codon 12 G12D and G12V and EGFR exon 21 L858R mutation, confirming the initial histologic impression. Subsequently, left upper lobe lobectomy showed 3 additional foci of adenocarcinoma with different morphologies, suggestive of synchronous primaries as well. No additional molecular testing was performed. Synchronous pulmonary adenocarcinomas are not uncommon; however, 4 or more synchronous tumors are rare. Distinguishing multiple primary tumors from intrapulmonary metastases is a common problem in thoracic oncology with major implications for staging, prognosis, and treatment. Lung adenocarcinoma subclassification based on predominant and coexisting histologic patterns can greatly facilitate differentiation between intrapulmonary metastases and multiple synchronous tumors. Use of molecular profiling is recommended since it further increases confidence in the diagnostic workup of multiple pulmonary adenocarcinomas and helps guiding therapy. © The Author(s) 2015.

Circumferential Peyronie's disease involving both the corpora cavernosa.

PubMed

Narita, T; Kudo, H; Matsumoto, K

1995-05-01

An extraordinary form of Peyronies disease is reported. The patient was a 52 year old male, who died of a malignant thymoma with multiple bone metastasis, extensive pleural carcinomatosis of the left lung and some metastatic nodules in the liver and the mesenterium. At autopsy, the proximal and middle portions of the penis were very hard. Macroscopically, the entire tunica albuginea of both the corpora cavernosa was markedly thickened, 2-4 mm; and calcified. Microscopically, the tunica albuginea showed extensive hyaline degeneration, calcification and ossifying foci with osteoblasts and osteoclasts. Inflammatory cells were frequently found beneath the thickened tunica albuginea. In the corpus cavernosum, cavernous arteries showed marked intimal thickening and medial muscular degeneration with a few inflammatory cells. Smooth muscles of the stroma were extensively atrophic and degenerative, and some of them were infiltrated with a few inflammatory cells. In the corpus spongiosum, the tunica albuginea was not thickened, but the smooth muscle in the stroma was atrophic and degenerative and a few inflammatory cells were also found. Surprisingly, there was no Littrés gland around the urethra. In Peyronies disease, the dorsal part of the penis is usually involved, and less frequently lateral or ventral sites are involved. The circumferential involvement of both the corpora cavernosa has not been reported until now, as far as the authors know.

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

PubMed Central

Tosi, Patrizia

2013-01-01

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. PMID:24381787

Trypanosoma cruzi infection induces a massive extrafollicular and follicular splenic B-cell response which is a high source of non-parasite-specific antibodies.

PubMed

Bermejo, Daniela A; Amezcua Vesely, María C; Khan, Mahmood; Acosta Rodríguez, Eva V; Montes, Carolina L; Merino, Maria C; Toellner, Kai Michael; Mohr, Elodie; Taylor, Dale; Cunningham, Adam F; Gruppi, Adriana

2011-01-01

Acute infection with Trypanosoma cruzi, the aetiological agent of Chagas' disease, results in parasitaemia and polyclonal lymphocyte activation. It has been reported that polyclonal B-cell activation is associated with hypergammaglobulinaemia and delayed parasite-specific antibody response. In the present study we analysed the development of a B-cell response within the different microenvironments of the spleen during acute T. cruzi infection. We observed massive germinal centre (GC) and extrafollicular (EF) responses at the peak of infection. However, the EF foci were evident since day 3 post-infection (p.i.), and, early in the infection, they mainly provided IgM. The EF foci response reached its peak at 11 days p.i. and extended from the red pulp into the periarteriolar lymphatic sheath. The GCs were detected from day 8 p.i. At the peak of parasitaemia, CD138(+) B220(+) plasma cells in EF foci, red pulp and T-cell zone expressed IgM and all the IgG isotypes. Instead of the substantial B-cell response, most of the antibodies produced by splenic cells did not target the parasite, and parasite-specific IgG isotypes could be detected in sera only after 18 days p.i. We also observed that the bone marrow of infected mice presented a strong reduction in CD138(+) B220(+) cells compared with that of normal mice. Hence, in acute infection with T. cruzi, the spleen appears to be the most important lymphoid organ that lodges plasma cells and the main producer of antibodies. The development of a B-cell response during T. cruzi infection shows features that are particular to T. cruzi and other protozoan infection but different to other infections or immunization with model antigens.

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

PubMed

Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

2018-05-21

While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an • OH pulse reduced to background the • OH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

Canine mammary minute oncocytomas with neuroendocrine differentiation associated with multifocal acinar cell oncocytic metaplasia.

PubMed

Nagahara, Rei; Kimura, Masayuki; Itahashi, Megu; Sugahara, Go; Kawashima, Masashi; Murayama, Hirotada; Yoshida, Toshinori; Shibutani, Makoto

2016-11-01

Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by microscopy in the left fourth mammary gland of a 13-year-old female Labrador Retriever dog, in addition to multiple mammary gland tumors. The former tumors were well circumscribed and were composed of small-to-large polyhedral neoplastic oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid nests separated by fine fibrovascular septa. Scattered lumina of variable sizes containing eosinophilic secretory material were evident. Cellular atypia was minimal, and no mitotic figures were visible. One tumor had several oncocytic cellular foci revealing cellular transition, with perivascular pseudorosettes consisting of columnar epithelial cells surrounding the fine vasculature. Scattered foci of mammary acinar cell hyperplasia showing oncocytic metaplasia were also observed. Immunohistochemically, the cytoplasm of neoplastic cells of the 2 microtumors showed diffuse immunoreactivity to anti-cytokeratin antibody AE1/AE3, and finely granular immunoreactivity for 60-kDa heat shock protein, mitochondrial membrane ATP synthase complex V beta subunit, and chromogranin A. One tumor also had oncocytic cellular foci forming perivascular pseudorosettes showing cellular membrane immunoreactivity for neural cell adhesion molecule. The tumors were negative for smooth muscle actin, neuron-specific enolase, vimentin, desmin, S100, and synaptophysin. Ultrastructural observation confirmed the abundant mitochondria in the cytoplasm of both neoplastic and hyperplastic cells, the former cells also having neuroendocrine granule-like electron-dense bodies. From these results, our case was diagnosed with mammary oncocytomas accompanied by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be related to the multicentric occurrence of these oncocytomas. © 2016 The Author(s).

Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma.

PubMed Central

Riccardi, A; Ucci, G; Luoni, R; Castello, A; Coci, A; Magrini, U; Ascari, E

1990-01-01

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance. Images PMID:2199532

Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-{beta} induction

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

Melroe, Gregory T.; Silva, Lindsey; Schaffer, Priscilla A.

2007-04-10

The host innate response to viral infection includes the production of interferons, which is dependent on the coordinated activity of multiple transcription factors. Herpes simplex virus 1 (HSV-1) has been shown to block efficient interferon expression by multiple mechanisms. We and others have demonstrated that HSV-1 can inhibit the transcription of genes promoted by interferon regulatory factor-3 (IRF-3), including interferon beta (IFN-{beta}), and that the immediate-early ICP0 protein is sufficient for this function. However, the exact mechanism by which ICP0 blocks IRF-3 activity has yet to be determined. Unlike some other viral proteins that inhibit IRF-3 activity, ICP0 does notmore » appear to affect phosphorylation and dimerization of IRF-3. Here, we show that a portion of activated IRF-3 co-localizes with nuclear foci containing ICP0 at early times after virus infection. Co-localization to ICP0-containing foci is also seen with the IRF-3-binding partners and transcriptional co-activators, CBP and p300. In addition, using immunoprecipitation of infected cell lysates, we can immunoprecipitate a complex containing ICP0, IRF-3, and CBP. Thus we hypothesize that ICP0 recruits activated IRF-3 and CBP/p300 to nuclear structures, away from the host chromatin. This leads to the inactivation and accelerated degradation of IRF-3, resulting in reduced transcription of IFN-{beta} and an inhibition of the host response. Therefore, ICP0 provides an example of how viruses can block IFN-{beta} induction by sequestration of important transcription factors essential for the host response.« less

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

PubMed Central

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

2012-01-01

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

Erysipelas in a free-ranging Hawaiian crow (Corvus hawaiiensis)

USGS Publications Warehouse

Work, Thierry M.; Ball, Donna; Wolcott, Mark

1999-01-01

We describe a case of erysipelas in a free-ranging endangered Hawaiian crow. The partially scavenged carcass exhibited gross emaciation and petechial hemorrhages in both lungs. Microscopy revealed multiple necrotic foci associated with gram-positive rods in the liver and adrenal, diffuse acute proximal tubular necrosis of kidney, diffuse necrosis and inflammation of proventricular mucosa associated with gram-positive rods, and multiple intravascular aggregates of gram-positive rods associated with thrombi. Culture of the kidney revealed the bacterium to be Erysipelothrix rhusiopathiae. The implications of this finding to free-ranging crows remain unclear.

Live Dynamics of 53BP1 Foci Following Simultaneous Induction of Clustered and Dispersed DNA Damage in U2OS Cells

PubMed Central

Sollazzo, Alice; Brzozowska, Beata; Cheng, Lei; Lundholm, Lovisa; Scherthan, Harry

2018-01-01

Cells react differently to clustered and dispersed DNA double strand breaks (DSB). Little is known about the initial reaction to simultaneous induction of DSBs with different complexities. Here, we used live cell microscopy to analyse the behaviour of 53BP1-GFP (green fluorescence protein) foci formation at DSBs induced in U2OS cells by alpha particles, X-rays or mixed beams over a 75 min period post irradiation. X-ray-induced foci rapidly increased and declined over the observation interval. After an initial increase, mixed beam-induced foci remained at a constant level over the observation interval, similarly as alpha-induced foci. The average areas of radiation-induced foci were similar for mixed beams and X-rays, being significantly smaller than those induced by alpha particles. Pixel intensities were highest for mixed beam-induced foci and showed the lowest level of variability over time as compared to foci induced by alphas and X-rays alone. Finally, mixed beam-exposed foci showed the lowest level of mobility as compared to alpha and X-ray exposure. The results suggest paralysation of chromatin around foci containing clustered DNA damage. PMID:29419809

A Call for More Religious Education in the Secondary Social Studies Curriculum of Western Canadian Provinces

ERIC Educational Resources Information Center

Patrick, Margaretta L.

2015-01-01

The inclusion of religion in public education remains contentious in many countries, including Canada. As multiple religions fill the public sphere, some religious education is necessary if Canadians are to understand each other. Social studies is seen as an appropriate subject to include such education given its foci on diversity and citizenship.…

When Simple Harmonic Motion Is Not that Simple: Managing Epistemological Complexity by Using Computer-Based Representations

ERIC Educational Resources Information Center

Parnafes, Orit

2010-01-01

Many real-world phenomena, even "simple" physical phenomena such as natural harmonic motion, are complex in the sense that they require coordinating multiple subtle foci of attention to get the required information when experiencing them. Moreover, for students to develop sound understanding of a concept or a phenomenon, they need to learn to get…

MRI Evaluation of Non-Necrotic T2-Hyperintense Foci in Pediatric Diffuse Intrinsic Pontine Glioma.

PubMed

Clerk-Lamalice, O; Reddick, W E; Li, X; Li, Y; Edwards, A; Glass, J O; Patay, Z

2016-05-19

The conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma. Twenty-five patients with diffuse intrinsic pontine gliomas were included in this study. MR imaging was performed at 3T by using conventional and advanced MR imaging sequences. Perfusion (CBV), vascular permeability (v e , K trans ), and diffusion (ADC) metrics were calculated and used to characterize non-necrotic T2-hyperintense foci in comparison with other lesion components, namely necrotic T2-hyperintense foci, T2-hypointense foci, peritumoral edema, and normal brain stem. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon rank sum tests. Sixteen non-necrotic T2-hyperintense foci were found in 12 tumors. In these foci, ADC values were significantly higher than those in either T2-hypointense foci (P = .002) or normal parenchyma (P = .0002), and relative CBV values were significantly lower than those in either T2-hypointense (P = .0002) or necrotic T2-hyperintense (P = .006) foci. Volume transfer coefficient values in T2-hyperintense foci were lower than those in T2-hypointense (P = .0005) or necrotic T2-hyperintense (P = .0348) foci. Non-necrotic T2-hyperintense foci are common, distinct lesion components within diffuse intrinsic pontine gliomas. Advanced MR imaging data suggest low cellularity and an early stage of angioneogenesis with leaky vessels resulting in expansion of the extracellular space. Because of the lack of biopsy validation, the underlying histoarchitectural and pathophysiologic changes remain unclear; therefore, these foci may correspond to a poorly understood biologic event in tumor evolution. © 2016 American Society of Neuroradiology.

Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias.

PubMed

Mitsiades, Constantine S; Rouleau, Cecile; Echart, Cinara; Menon, Krishna; Teicher, Beverly; Distaso, Maria; Palumbo, Antonio; Boccadoro, Mario; Anderson, Kenneth C; Iacobelli, Massimo; Richardson, Paul G

2009-02-15

Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation-related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappaB activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in combination with conventional and novel therapies to potentially improve patient outcome in multiple myeloma and other malignancies.

Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy.

PubMed

Kleber, Martina; Udi, Josefina; Metzke, Barbara; Terpos, Evangelos; Roodmann, G David; Morgan, Gareth; Dispenzieri, Angela; Einsele, Hermann; Wäsch, Ralph; Engelhardt, Monika

2012-06-01

An international myeloma meeting entitled "Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy" was held in Freiburg, Germany in July 2011 to discuss novel insights into and approaches to myeloma bone disease and other bone-seeking tumors. This review briefly summarizes the most prominent data of the meeting and current literature on our understanding of bone disease, the role of imaging techniques, operative interventions and systemic bone-seeking treatment, all of which should further improve our future therapeutic choices.

Meiotic recombination and spermatogenic impairment in Mus musculus domesticus carrying multiple simple Robertsonian translocations.

PubMed

Merico, V; Pigozzi, M I; Esposito, A; Merani, M S; Garagna, S

2003-01-01

We quantitatively analyzed the spermatogenic process, including evaluation of seminiferous tubules with defective cycles, rates of germ cell death and sperm morphology, in adult male mice with standard telocentric chromosomes (2n = 40, CD1 strain), homozygous (2n = 24, Mil II population) and heterozygous (2n = 24 x 40) for Robertsonian (Rb) rearrangements. The animals were analyzed at three different ages: three, five and seven months after birth. The number and position of crossover events were also determined by chiasmata counting and immunostaining with an antibody against mouse MLH1 protein. Our analysis of spermatogenesis confirms the impairment of the spermatogenic process in multiple simple heterozygotes due to both germ cell and abnormal sperm morphology. The detrimental effects exerted by Rb heterozygosities were found to be at least partially buffered with time: the frequency of defective tubules was lower and germ cell survival and sperm morphology better in 7-month-old animals than in the 3- and 5-month-old mice. While there are previously published data on germ cell death in multiple simple heterozygotes, this is the first report of a partial rescue of spermatogenesis with time. The mean frequency of MLH1 foci was lower in Rb homozygous and heterozygous mice than in mice carrying all telocentric chromosomes. The lower number of foci in Rb mice can be ascribed to a decrease in the number of multiple chiasmata and the maintenance of single chiasmata preferentially located in the terminal region of both the telocentric and metacentric chromosomes. Copyright 2003 S. Karger AG, Basel

Reassignment of scattered emission photons in multifocal multiphoton microscopy.

PubMed

Cha, Jae Won; Singh, Vijay Raj; Kim, Ki Hean; Subramanian, Jaichandar; Peng, Qiwen; Yu, Hanry; Nedivi, Elly; So, Peter T C

2014-06-05

Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image.

On-axis non-linear effects with programmable Dammann lenses under femtosecond illumination.

PubMed

Pérez Vizcaíno, Jorge; Mendoza-Yero, Omel; Borrego-Varillas, Rocío; Mínguez-Vega, Gladys; Vázquez de Aldana, Javier R; Láncis, Jesús

2013-05-15

We demonstrate the utilization of Dammann lenses codified onto a spatial light modulator (SLM) for triggering non-linear effects. With continuous wave illumination Dammann lenses are binary phase optical elements that generate a set of equal intensity foci. We theoretically calculate the influence of ultrashort pulse illumination on the uniformity of the generated pattern, which is affected by chromatic aberration for pulses with temporal widths lower than 100 fs. The simulations also indicate that acceptable uniformity can be achieved for pulses of several fs by shortening the distance among foci which can be easily modified with the SLM. Multifocal second-harmonic generation (SHG) and on-axis multiple filamentation are produced and actively controlled in β-BaB2O4 (BBO) and fused silica samples, respectively, with an amplified Ti: Sapphire femtosecond laser of 30 fs pulse duration. Experimental results are in very good agreement with theoretical calculations.

Poly(A)-binding proteins and mRNA localization: who rules the roost?

PubMed

Gray, Nicola K; Hrabálková, Lenka; Scanlon, Jessica P; Smith, Richard W P

2015-12-01

RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals. © 2015 Authors; published by Portland Press Limited.

Aging of hematopoietic stem cells: DNA damage and mutations?

PubMed

Moehrle, Bettina M; Geiger, Hartmut

2016-10-01

Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly larger amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared with young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase in and nature of DNA mutations in the hematopoietic system with age, the quality of the DNA damage response in aged HSCs, and the nature of γH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or three-dimensional architecture of the cell as major cell intrinsic factors of HSCs aging. Aging of HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSC aging in the light of these novel mechanisms of aging of HSCs. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

The occurrence and pathogenicity of Serratospiculum tendo (Nematoda: Diplotriaenoidea) in birds of prey from southern Italy.

PubMed

Santoro, M; D'Alessio, N; Di Prisco, F; Kinsella, J M; Barca, L; Degli Uberti, B; Restucci, B; Martano, M; Troisi, S; Galiero, G; Veneziano, V

2016-05-01

The air sacs of free-ranging birds of prey (n= 652) from southern Italy, including 11 species of Accipitriformes and six of Falconiforms, were examined for infections with Serratospiculum tendo (Nematoda: Diplotriaenoidea). Of the 17 species of birds examined, 25 of 31 (80.6%) peregrine falcons (Falco peregrinus) from Calabria Region and a single northern goshawk (Accipiter gentilis) from Campania Region were infected with S. tendo, suggesting a strong host specificity for the peregrine falcon. The northern goshawk and 18 of 25 infected peregrine falcons showed cachexia and all infected birds had bone fractures. At gross examination, air sacculitis and pneumonia were the most common lesions in infected birds. Microscopically, the air-sac walls showed thickening of the smooth muscle cells, resulting in a papillary appearance, along with hyperplasia of the mesothelium and epithelium, and foci of plasma cell infiltration and macrophages associated with several embryonated eggs and adult parasites. Extensive areas of inflammation were found in the lungs, characterized by lymphocytes, macrophages and fibroblasts surrounding embryonated eggs. The northern goshawk also had detachment of the dextral lung with several necrotic foci. In this case, the death of the bird was directly attributed to S. tendo infection. Lesions and pathological changes observed here suggest that S. tendo can cause disease.

γH2AX foci on apparently intact mitotic chromosomes: Not signatures of misrejoining events but signals of unresolved DNA damage

PubMed Central

Martín, Marta; Terradas, Mariona; Hernández, Laia; Genescà, Anna

2014-01-01

The presence of γH2AX foci on apparently intact mitotic chromosomes is controversial because they challenge the assumed relationship between γH2AX foci and DNA double-strand breaks (DSBs). In this work, we show that after irradiation during interphase, a variety of γH2AX foci are scored in mitotic cells. Surprisingly, approximately 80% of the γH2AX foci spread over apparently undamaged chromatin at Terminal or Interstitial positions and they can display variable sizes, thus being classified as Small, Medium and Big foci. Chromosome and chromatid breaks that reach mitosis are spotted with Big (60%) and Medium (30%) Terminal γH2AX foci, but very rarely are they signaled with Small γH2AX foci. To evaluate if Interstitial γH2AX foci might be signatures of misrejoining, an mFISH analysis was performed on the same slides. The results show that Interstitial γH2AX foci lying on apparently intact chromatin do not mark sites of misrejoining, and that misrejoined events were never signaled by a γH2AX foci during mitosis. Finally, when analyzing the presence of other DNA-damage response (DDR) factors we found that all γH2AX foci—regardless their coincidence with a visible break—always colocalized with MRE11, but not with 53BP1. This pattern suggests that these γH2AX foci may be hallmarks of both microscopically visible and invisible DNA damage, in which an active, although incomplete or halted DDR is taking place. PMID:25486563

All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision.

PubMed

de Mascarel, Isabelle; Brouste, Véronique; Asad-Syed, Maryam; Hurtevent, Gabrielle; Macgrogan, Gaëtan

2011-09-01

The necessity of excision is debatable when atypia are diagnosed at stereotactic vacuum-assisted breast biopsy (microbiopsy). Among the 287 surgical excisions performed at Institut Bergonié from 1999 to 2009, we selected a case-control study group of 151 excisions; 52 involving all the diagnosed cancers and 99 randomly selected among the 235 excisions without cancer, following atypical microbiopsy (24 flat epithelial atypia; 50 atypical ductal hyperplasia; 14 lobular neoplasia; 63 mixed lesions). Mammographical calcification (type, extension, complete removal) and histological criteria of epithelial atypia (type, number of foci, size/extension), topography and microcalcification extension at microbiopsy were compared according to the presence or absence of cancer at excision. Factors associated with cancer at excision were Breast Imaging Reporting and Data System (BI-RADS5) lesions, large and/or multiple foci of mammographical calcifications, histological type, number, size and extension of atypical foci. Flat epithelial atypia alone was never associated with cancer at excision. BI-RADS5, atypical ductal hyperplasia (alone or predominant) and >3 foci of atypia were identified as independent pejorative factors. There was never any cancer at excision when these pejorative factors were absent (n=31). Presence of one (n=59), two (n=23) or three (n=14) factors was associated with cancer in 24, 15 and 13 cases with an odds ratio=5.8 (95% CI: 3-11.2) for each additional factor. We recommend that mammographical data and histological characteristics be taken into account in the decision-making process after diagnosis of atypia on microbiopsy. With experienced senologists and strict histological criteria, some patients could be spared surgery resulting in significant patient, financial and time advantages.

Simultaneous Biatrial High-Density (510-512 Electrodes) Epicardial Mapping of Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: New Insights Into the Mechanism of Its Maintenance.

PubMed

Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Cakulev, Ivan; Markowitz, Alan; Waldo, Albert L

2015-12-01

The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high-density, simultaneous, biatrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (1) to test the hypothesis that persistent and LSP AF are due to ≥ 1 drivers, either focal or reentrant, and (2) to characterize associated atrial activation. Twelve patients with persistent and LSP AF (1 month to 9 years duration) were studied at open heart surgery. During AF, electrograms were recorded from both atria simultaneously for 1 to 5 minutes from 510 to 512 epicardial electrodes with ECG lead II. Thirty-two consecutive seconds of activation sequence maps were produced per patient. During AF, multiple foci (QS unipolar atrial electrograms) of different cycle lengths (mean, 175 ± 18 ms) were present in both atria in 11 of 12 patients. Foci (2-4 per patient, duration 5-32 s) were either sustained or intermittent, were predominantly found in the lateral left atrial free wall, and likely acted as drivers. Random and nonrandom breakthrough activation sites (initial r or R in unipolar atrial electrograms) were also found. In 1 of 12 patients, only breakthrough sites were found. All wave fronts emanated from foci and breakthrough sites, and largely either collided or merged with each other at variable sites. Repetitive focal QS activation occasionally generated repetitive wannabe reentrant activation in 5 of 12 patients. No actual reentry was found. During persistent and LSP AF in 12 patients, wave fronts emanating from foci and breakthrough sites maintained AF. No reentry was demonstrated. © 2015 American Heart Association, Inc.

History of hyperthyroidism and long-term outcome of catheter ablation of drug-refractory atrial fibrillation.

PubMed

Wongcharoen, Wanwarang; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Chong, Eric; Chao, Tze-Fan; Tuan, Ta-Chuan; Chang, Yao-Ting; Lin, Chin-Yu; Liao, Jo-Nan; Lin, Yi-Chun; Chen, Yun-Yu; Chen, Shih-Ann

2015-09-01

Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status. The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism. The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients. Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P < .01), and higher prevalence of non-PV foci (42% vs 23%, P < .01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P < .01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history. Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Maintaining Bone Health in Patients With Multiple Myeloma: Survivorship Care Plan of the International Myeloma Foundation Nurse Leadership Board

PubMed Central

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

2014-01-01

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. PMID:21816707

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

PubMed

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.

[Mechanisms for the formation of a combination of the natural foci of trematodiases and tularemia in the floodplain-river ecosystem of the Konda River in different periods of epizootic activity of an infection focus].

PubMed

Ushakov, A V

2011-01-01

The basis of the mechanism responsible for the formation of a combination of the natural foci of trematodiases and tularemia in the infection foci in the interepizootic periods is their association with the morphological structure of the floodplain-river landscape of the Konda River. The landscape's facias and holes, which are common to the foci, are integrated, by predetermining the territorial combination. The formation of a closed trinomial Francisella tularensis parasite system integrating these foci serves as a basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia on transition of the latter from the interepizootic state to epizooty. The absence of host populations linking the foci of methorchiasis (M. xanthosomus), bilharziasis, and tularemia determines their combination both in the interepizootic periods and at the level of the landscape morphological structure. The basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia in the periods of diffuse epizooties in the infection foci is the formation of an open binomial F. tularensis parasite system and the infestation of the co-members of F. tularensis trematode parasite systems. By penetrating into them, the pathogen forces the F. tularensis parasite system to enter the trematode parasite systems, causing their complete (opisthorchiases, methorchiases) or partial (bilharziasis) coincidence. Thus, these foci are combined at the level of parasitocenoses of the parasite systems of infections and infestations, by giving rise to pseudosystem combined foci. The natural foci of B. polonica and F. tularensis are combined at the level of parasitocenosis of the coacting hemipopulation of trematode parthenitas, F. tularensis subpopulations and intermediate host population, by forming an autoecious population-combination bilharziasis-tularemia focus. The formation of territorial-combination, autoecious population-combination, and pseudosystem-combination foci of trematodiases and tularemia in different periods of the epizootic activity of an infection focus is determined by the functional organization of the parasite system of a tularemia focus and the biocenotic (functional) structure of natural foci of infestations.

A Protocol Analysis of the Influence of Technology on Students' Actions, Verbal Commentary, and Thought Processes During the Performance of Acid-Base Titrations.

ERIC Educational Resources Information Center

Nakhleh, Mary B.; Krajcik, Joseph S.

1993-01-01

From an analysis of 14 secondary student's actions and thought processes, it was found that technology's level of information affected the focus of student observations. The microcomputer group focused primarily on the graph while other groups exhibited multiple foci. The discussion data also reveal that students have three main ideas about how…

Mapping transmission foci to eliminate malaria in the People's Republic of China, 2010-2015: a retrospective analysis.

PubMed

Feng, Jun; Tu, Hong; Zhang, Li; Zhang, Shaosen; Jiang, Shan; Xia, Zhigui; Zhou, Shuisen

2018-03-07

China has initiated the National Malaria Elimination Action Plan, which aims to eliminate malaria by 2020. However, the transmission of malaria occurs sporadically or in distinct foci, which greatly hampers progress toward elimination in China and other countries. The object of this study was to foci categorization and evaluates whether the response met the requirements issued by the nation or WHO. Residual transmissions were investigated and located with fine spatial resolution mapping from parasitological confirmed malaria cases by use of routine national surveillance data. The "1-3-7" timeframes were monitored for each focus between 2012 and 2015. Each focus was identified, and the application of appropriate measures was evaluated. A total of 5996 indigenous cases were recorded between 2010 and 2015; during this period, the number of cases declined by 99.1% (2010, n = 4262; 2015, n = 39). Most indigenous cases (92.5%) were reported in Anhui (n = 2326), Yunnan (n = 1373), Henan (n = 930), Hubei (n = 459), and Guizhou (n = 458). The temporal distribution showed that the indigenous malaria cases were clustered during the period of May to August. A total of 320 foci were carefully investigated and analyzed: 24 were active foci; 72, residual non-active foci; and 224 cleared-up foci. For the foci response evaluation, all the active foci were investigated within 7 days, while 80.2% of the residual non-active foci were responded within 7 days. In addition, reactive case detection (RACD) was carried out with 92.9% of the active foci and vector investigation carried out with 75%. For residual non-active foci, RACD was carried out with 83.2% and vector investigation with 78.2% of the foci. This study used nationwide data to categorize foci in China and evaluate the response of these areas during the control and elimination phases. Our approach stratifies future control responses by identifying those locations where the elimination of endemic transmission is needed, such as in the counties at the China-Myanmar border and in Tibet. In addition, this study will help local CDC staff to reassess their needs and responses against different types of foci during the elimination and post-elimination phases.

Impaired ambulation and steroid therapy impact negatively on bone health in multiple sclerosis.

PubMed

Tyblova, M; Kalincik, T; Zikan, V; Havrdova, E

2015-04-01

The prevalence of osteopenia and osteoporosis is higher amongst patients with multiple sclerosis in comparison with the general population. In addition to the general determinants of bone health, two factors may contribute to reduced bone mineral density in multiple sclerosis: physical disability and corticosteroid therapy. The aim of this study was to examine the effect of physical disability and steroid exposure on bone health in weight-bearing bones and spine and on the incidence of low-trauma fractures in multiple sclerosis. In this retrospective analysis of prospectively collected data, associations between bone mineral density (at the femoral neck, total femur and the lumbar spine) and its change with disability or cumulative steroid dose were evaluated with random-effect models adjusted for demographic and clinical determinants of bone health. The incidence of low-trauma fractures during the study follow-up was evaluated with Andersen-Gill models. Overall, 474 and 438 patients were included in cross-sectional and longitudinal analyses (follow-up 2347 patient-years), respectively. The effect of severely impaired gait was more apparent in weight-bearing bones (P ≤ 10(-15) ) than in spine (P = 0.007). The effect of cumulative steroid dose was relatively less pronounced but diffuse (P ≤ 10(-4) ). Risk of low-trauma fractures was associated with disability (P = 0.02) but not with cumulative steroid exposure and was greater amongst patients with severely impaired gait (annual risk 3.5% vs. 3.0%). Synergistic effects were found only between cumulative steroid dose in patients ambulatory without support (P = 0.02). Bone health and the incidence of low-trauma fractures in multiple sclerosis are more related to impaired gait than to extended corticosteroid therapy. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

NASA Technical Reports Server (NTRS)

Ponomarev, Artem; Cucinotta, F.

2011-01-01

To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantization of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiments using proteins that detect DNA damage. An automated image segmentaiton software can prove useful in a faster and more precise object counting for colocolized foci images.

[The results of serological studies in different foci of tropical and tertiary malaria].

PubMed

Suleĭmanov, G D; Doan, Kh N; Le, T T; Chan, B; Chan, T U

1991-01-01

Attempt was made to determine the value of serologic indices of malaria surveys. Following uniformed methodological and technical approaches 3 foci of P. vivax and 6 foci of P. falciparum malaria were surveyed in different endemic zones of Vietnam and the USSR. It was shown that the most objective criteria for a foci classification is its serologic mean geometric titre. The latter in its turn directly depends of transmission longevity in a foci.

Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review of Literature.

PubMed

Gupta, Monica; Singhal, Lalita; Kumar, Akshay

2018-06-01

Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.

[Correlative factors related to the density of Meriones unguiculatus in the Meriones unguiculatus plague foci of Hebei province, 2001-2013].

PubMed

Niu, Y F; Kang, X P; Yan, D; Zhang, Y H; Liu, G; Kang, D M; Liu, H Z; Shi, X M; Li, Y G

2016-08-10

To explore the yearly, monthly and habitat-related distribution and their relations with Meriones unguiculatus density in the Hebei Meriones unguiculatus plague foci, from 2001 to 2013. Data related to Meriones unguiculatus was gathered through the monitoring programs set up at the national and provincial Meriones unguiculatus plague foci in Hebei province, from 2001 to 2013. According to the yearly density of Meriones unguiculatus, criteria set for the three groups under study, were as follows:'high-risk group'-when the rodent density was≥1.00 under rodents/hm(2),'warning group'-when the rodents/hm(2)>rodent density> 0.20,'standard group'-when rodents/hm(2) rodent density≤0.20 rodents/hm(2). Differences of habitats and monthly distribution among the three groups were compared, under the Kruskal-Wallis H rank sum test while their relations were under the multiple correspondence analysis. The Meriones unguiculatus densities were higher than 1.00 rodents/hm(2), far above the set national standards, in the monitoring area, between 2001 and 2005. From 2005, though the rodent densities began to decrease, however, figures from 2008 to 2013 were still among 0.20 to 1.00 rodents/hm(2). The distribution of habitats in the three groups showed that the Meriones unguiculatus densities were all different in habitats and the difference was statistically significant (P<0.05). The highest median densities were all in the arable land, with maximum value of high-risk group appeared the highest (20.50 rodents/hm(2)) in the wasteland. Monthly distribution showed that the Meriones unguiculatus densities were different and the difference was statistically significant (P<0.05) in the high-risk and standard groups but not statistically significant in the warning group. Data from the multiple correspondence analysis showed that there was a strong aggregation among wasteland, in April and June, while the warning group was associated with weather in July and the arable land. When the density became higher than 1.00 rodents/hm(2), the risk on animal plague increased in Hebei Meriones unguiculatus plague foci. Based on the distribution of Meriones unguiculatus, programs should be set to monitor the rodent in arable land and wasteland, in April and June, to reduce the prevalence of animals plague.

Early Sonographic Diagnosis of Neurocutaneous Melanosis in a Newborn

PubMed Central

Yakut, Zeynep Ilerisoy; Bas, Ahmet Yagmur; Turan, Aynur; Demirel, Nihal; Demirkan, Tulin Hakan

2014-01-01

Neurocutaneous melanosis (NCM) is a rare, congenital non-hereditary syndrome, characterized by multiple pigmented nevi. We report the radiologic findings of a newborn who had extensive cutaneous melanotic nevus with satellite lesions in the brain. Ultrasound showed multiple echogenic foci in the cerebral parenchyma. Subsequent MRI confirmed these lesions as characteristic deposits of melanin. The infant was asymptomatic, but presence of risk factors such as malign transformation or neurological manifestations makes early diagnosis very important. We present this case to emphasize on the radiological findings of this syndrome in order to reach an early diagnosis. PMID:25780540

Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation.

PubMed

Yoshikawa, Y; Yamasaki, A; Takatori, K; Suzuki, M; Kobayashi, J; Takao, M; Zhang-Akiyama, Q-M

2015-10-01

Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H2O2), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H2O2. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH(•), and H2O2, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H2O2 induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability.

Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization.

PubMed

Holm, Erik; Aubin, Jane E; Hunter, Graeme K; Beier, Frank; Goldberg, Harvey A

2015-02-01

Bone sialoprotein (BSP) is an anionic phosphoprotein in the extracellular matrix of mineralized tissues, and a promoter of biomineralization and osteoblast development. Previous studies on the Bsp-deficient mouse (Bsp(-/-)) have demonstrated a significant bone and periodontal tissue phenotype in adulthood. However, the role of BSP during early long bone development is not known. To address this, early endochondral ossification in the Bsp(-/-) mouse was studied. Embryonic day 15.5 (E15.5) wild-type (WT) tibiae showed early stages of ossification that were absent in Bsp(-/-) mice. At E16.5, mineralization had commenced in the Bsp(-/-) mice, but staining for mineral was less intense and more dispersed compared with that in WT controls. Tibiae from Bsp(-/-) mice also demonstrated decreased mineralization and shortened length at postnatal day 0.5 (P0.5) compared to WT bones. There was no detectable difference in the number of tartrate-resistant acid phosphatase-positive foci at P0.5, although the P0.5 Bsp(-/-) tibiae had decreased Vegfα expression compared with WT tissue. Due to the shortened tibiae the growth plates were examined and determined to be of normal overall length. However, the length of the resting zone was increased in P0.5 Bsp(-/-) tibiae whereas that of the proliferative zone was decreased, with no change in the hypertrophic zone length of Bsp(-/-) mice. A reduction in cells positive for Ki-67, an S-phase cell-cycle marker, was noted in the proliferative zone. Decreased numbers of TUNEL-positive hypertrophic chondrocytes were also apparent in the Bsp(-/-) tibial growth plates, suggesting decreased apoptosis. Expression of the osteogenic markers Alp1, Col1a1, Sp7, Runx2, and Bglap was reduced in the endochondral bone of the neonatal Bsp(-/-) compared to WT tibiae. These results suggest that BSP is an important and multifaceted protein that regulates both chondrocyte proliferation and apoptosis as well as transition from cartilage to bone during development of endochondral bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene.

PubMed

Park, Jung-Young; Virts, Elizabeth L; Jankowska, Anna; Wiek, Constanze; Othman, Mohamed; Chakraborty, Sujata C; Vance, Gail H; Alkuraya, Fowzan S; Hanenberg, Helmut; Andreassen, Paul R

2016-10-01

Fanconi anaemia (FA) is a heterogeneous inherited disorder clinically characterised by progressive bone marrow failure, congenital anomalies and a predisposition to malignancies. Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Cells (900677A) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage and G2-M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harboured by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677A cells have reduced levels of other proteins in the XRCC2-RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677A cells. Thus, XRCC2 acts late in the FA-BRCA pathway as also suggested by hypersensitivity of 900677A cells to ionising radiation. These cells also share milder sensitivities towards olaparib and formaldehyde with certain other FA cells. XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[Multistep surgery for spondylosyndesis. Treatment concept of destructive spondylodiscitis in patients with reduced general condition].

PubMed

Isenberg, J; Jubel, A; Hahn, U; Seifert, H; Prokop, A

2005-02-01

Retrospective assessment of multistage surgery in the treatment of progressive spondylodiscitis in patients with critical physical status. A total of 34 patients (mean age 58.6 years) with 37 progressive spondylodiscitis foci and destruction of one to three vertebral segments (1.9 mean) were recorded within an 8-year period. Time between first complaints and operative treatment was 3 months (mean). Preoperative health status was critically reduced in 11 patients (ASA IV) and poor general condition (ASA III) was seen in 23 patients when vital indication was seen preoperatively. Considerable systemic disease (n=31), further infection focus (n=18), and nosocomial trauma (n=5) were causally related. Spondylodiscitis was seen more frequently in the lumbar (n=20) and thoracolumbar than in the thoracic (n=10) and cervical spine (n=1). Staphylococcus aureus was detectable from operative specimens and hemoculture in 15 cases, MRSA in 6 of these. In cases of monosegmentary involvement (n=7) ventral debridement, biopsy, and application of antibiotic chains were followed by autologous interbody bone grafting in a second stage operation. In 29 cases with destruction of two (n=27) and three (n=3) segments, posterior instrumentation including laminectomy in 4 patients was completed by anterior debridement and application of antibiotic chains during a first surgical intervention. After stabilization of physical condition and having reached a macroscopically indisputable implant bed, the ventral fusion with autologous interbody bone grafting or cage in combination with a plate or internal fixation system was performed as the last of several surgical steps. No case of perioperative mortality was observed. Intensive care continued 9.1 days and hospitalization 49.5 days (mean). During a 37.6-month follow-up two late recurrences were observed. A multistep surgical procedure under protection of dorsal instrumentation can limit perioperative mortality in patients in critical general condition by avoiding an extended one stage dorsoventral spondylodesis. After eradication of further infection foci and stabilization of physical condition, ventral instrumentation is completed under elective conditions.

Coexistence of Multiple Attractors in an Active Diode Pair Based Chua’s Circuit

NASA Astrophysics Data System (ADS)

Bao, Bocheng; Wu, Huagan; Xu, Li; Chen, Mo; Hu, Wen

This paper focuses on the coexistence of multiple attractors in an active diode pair based Chua’s circuit with smooth nonlinearity. With dimensionless equations, dynamical properties, including boundness of system orbits and stability distributions of two nonzero equilibrium points, are investigated, and complex coexisting behaviors of multiple kinds of disconnected attractors of stable point attractors, limit cycles and chaotic attractors are numerically revealed. The results show that unlike the classical Chua’s circuit, the proposed circuit has two stable nonzero node-foci for the specified circuit parameters, thereby resulting in the emergence of multistability phenomenon. Based on two general impedance converters, the active diode pair based Chua’s circuit with an adjustable inductor and an adjustable capacitor is made in hardware, from which coexisting multiple attractors are conveniently captured.

[Infection and sickle cell anemia].

PubMed

Bégué, P

1999-01-01

Sickle cell disease is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumococcal bacteremia and meningitis are so severe as to warrant prophylactic penicillin therapy, which has provided a dramatic decrease in early mortality. Bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia. Osteomyelitis is generally due to a salmonella, most often S. enteritidis; multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Parvovirus B 19 infection causes acute bone marrow failure. Malaria does not result in cerebral malaria but can lead to severe anemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (septicemia, meningitis, osteomyelitis), and mycoplasmas (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at four months of age and on closely-spaced immunizations, most notably against pneumococci, the hepatitis B virus, S. typhi, and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. Conjugated pneumococcal vaccines are effective in protecting infants and should therefore be used in sickle cell patients.

Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to ⁶⁰Co γ-rays and p(66)+ Be(40) neutrons.

PubMed

Vandersickel, Veerle; Beukes, Philip; Van Bockstaele, Bram; Depuydt, Julie; Vral, Anne; Slabbert, Jacobus

2014-02-01

To investigate both the formation of micronuclei (MN) and the induction and subsequent loss of phosphorylated histone H2AX foci (γH2AX foci) after in vitro exposure of human lymphocytes to either (60)Co γ-rays or p(66)+ Be(40) neutrons. MN dose response (DR) curves were obtained by exposing isolated lymphocytes of 10 different donors to doses ranging from 0-4 Gy γ-rays or 0-2 Gy neutrons. Also, γH2AX foci DR curves were obtained following exposure to doses ranging from 0-0.5 Gy of either γ-rays or neutrons. Foci kinetics for lymphocytes for a single donor exposed to 0.5 Gy γ-rays or neutrons were studied up to 24 hours post-irradiation. Micronuclei yields following neutron exposure were consistently higher compared to that from (60)Co γ-rays. All MN yields were over-dispersed compared to a Poisson distribution. Over-dispersion was higher after neutron irradiation for all doses > 0.1 Gy. Up to 4 hours post-irradiation lower yields of neutron-induced γH2AX foci were observed. Between 4 and 24 hours the numbers of foci from neutrons were consistently higher than that from γ-rays. The half-live of foci disappearance is only marginally longer for neutrons compared to that from γ-rays. Foci formations were more likely to be over-dispersed for neutron irradiations. Although neutrons are more effective to induce MN, the absolute number of induced γH2AX foci are less at first compared to γ-rays. With time neutron-induced foci are more persistent. These findings are helpful for using γH2AX foci in biodosimetry and to understand the repair of neutron-induced cellular damage.

Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model.

PubMed

Hara, Shintaro; Morita, Reiko; Ogawa, Takashi; Segawa, Risa; Takimoto, Norifumi; Suzuki, Kazuhiko; Hamadate, Naobumi; Hayashi, Shim-Mo; Odachi, Ayano; Ogiwara, Isao; Shibusawa, Sakae; Yoshida, Toshinori; Shibutani, Makoto

2014-08-01

To investigate the protective effect of bilberry extracts (BBE) and enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We examined the modifying effect of co-administration with BBE or EMIQ on the liver tissue environment including oxidative stress responses, cell proliferation and apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth factor (TGF)-β/Smad signalings on the induction mechanism of preneoplastic lesions during early stages of hepatocellular tumor promotion. PBO increased the numbers and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of Ki-67(+) proliferating cells within GST-P(+) foci. Co-administration of BBE or EMIQ suppressed these effects with the reductions of GST-P(+) foci (area) to 48.9-49.4% and Ki-67(+) cells to 55.5-61.4% of the PBO-promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid-reactive substances to 78.4% of the PBO-promoted cases. PBO increased the incidences of phospho-PTEN(-) foci, phospho-Akt substrate(+) foci, phospho-Smad3(-) foci and Smad4(-) foci in GST-P(+) foci. Both BBE and EMIQ decreased the incidences of phospho-PTEN(-) foci in GST-P(+) foci to 59.8-72.2% and Smad4(-) foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the incidence of phospho-Akt substrate(+) foci in GST-P(+) foci to 75.2-75.7% of the PBO-promoted cases. These results suggest that PBO-induced tumor promotion involves facilitation of PTEN/Akt and disruptive TGF-β/Smad signalings without relation to oxidative stress responses, but this promotion was suppressed by co-treatment with BBE or EMIQ through suppression of cell proliferation activity of preneoplastic liver cells. Copyright © 2014 Elsevier GmbH. All rights reserved.

Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.

PubMed

Vos, Fidel J; Kullberg, Bart Jan; Sturm, Patrick D; Krabbe, Paul F M; van Dijk, Arie P J; Wanten, Geert J A; Oyen, Wim J G; Bleeker-Rovers, Chantal P

2012-03-01

Early detection of metastatic infection in patients with Gram-positive bacteremia is important as morbidity and mortality are higher in the presence of these foci, probably due to incomplete eradication of clinically silent foci during initial treatment. We performed a prospective study in 115 patients with Staphylococcus aureus or Streptococcus species bacteremia with at least 1 risk factor for the development of metastatic foci, such as community acquisition, treatment delay, persistently positive blood cultures for >48 hours, and persistent fever >72 hours after initiation of treatment. An intensive search for metastatic infectious foci was performed including ¹⁸F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomography scanning for optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first 2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%) patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. The incidence of metastatic infection was similar in patients with Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms guiding the attending physician in the diagnostic workup were present in only a minority of cases (41%). An unknown portal of entry, treatment delay >48 hours, and the presence of foreign body material were significant risk factors for developing metastatic foci. Mean C-reactive protein levels on admission were significantly higher in patients with metastatic infectious foci (74 vs. 160 mg/L). FDG-PET/CT was the first technique to localize metastatic infectious foci in 35 of 115 (30%) patients. As only a minority of foci were accompanied by guiding signs or symptoms, the number of foci revealed by symptom-guided CT, ultrasound, and magnetic resonance imaging remained low. Mortality tended to be lower in patients without complicated infection compared to those with metastatic foci (16% vs. 25%, respectively). Five of 31 patients (16%) without proven metastatic foci died. In retrospect, 3 of these 5 patients likely had metastatic foci that could not be diagnosed while alive. In patients with Gram-positive bacteremia and a high risk of developing complicated infection, a structured protocol including echocardiography and FDG-PET/CT aimed at detecting metastatic infectious foci can contribute to improved outcome.

Repression of Multiple Myeloma Growth and Preservation of Bone with Combined Radiotherapy and Anti-angiogenic Agent

PubMed Central

Jia, Dan; Koonce, Nathan A.; Halakatti, Roopa; Li, Xin; Yaccoby, Shmuel; Swain, Frances L.; Suva, Larry J.; Hennings, Leah; Berridge, Marc S.; Apana, Scott M.; Mayo, Kevin; Corry, Peter M.; Griffin, Robert J.

2011-01-01

The effects of ionizing radiation, with or without the antiangiogenic agent anginex (Ax), on multiple myeloma growth were tested in a SCID-rab mouse model. Mice carrying human multiple myeloma cell-containing pre-implanted bone grafts were treated weekly with various regimens for 8 weeks. Rapid multiple myeloma growth, assessed by bioluminescence intensity (IVIS), human lambda Ig light chain level in serum (ELISA), and the volume of bone grafts (caliper), was observed in untreated mice. Tumor burden in mice receiving combined therapy was reduced to 59% (by caliper), 43% (by ELISA), and 2% (by IVIS) of baseline values after 8 weeks of treatment. Ax or radiation alone slowed but did not stop tumor growth. Four weeks after the withdrawal of the treatments, tumor burden remained minimal in mice given Ax + radiation but increased noticeably in the other three groups. Multiple myeloma suppression by Ax + radiation was accompanied by a marked decrease in the number and activity of osteoclasts in bone grafts assessed by histology. Bone graft integrity was preserved by Ax + radiation but was lost in the other three groups, as assessed by microCT imaging and radiography. These results suggest that radiotherapy, when primed by anti-angiogenic agents, may be a potent therapy for focal multiple myeloma. PMID:20518660

Orthodontic treatment for oral rehabilitation after multiple maxillofacial bone fractures.

PubMed

Nakamura, Yoshiki; Ogino, Tomoko Kuroiwa; Hirashita, Ayao

2008-09-01

We present the orthodontic treatment of a patient with occlusal dysfunction after plastic surgery for multiple maxillofacial bone fractures caused by a traffic accident. The patient had mandibular deviation to the right because of inappropriate repositioning and fixation of the fractured bone and complete avulsion of both mandibular central incisors. The bilateral mandibular incisors, canines, and premolars were also suspected of partial avulsion or alveolar bone fracture. Several tests, including percussion and dental computed tomography, were performed on these teeth to rule out ankylosis and confirm tooth movement. Camouflage orthodontic treatment was carried out with expansion of the maxillary arch, alignment of both arches, and space closure between the mandibular lateral incisors to improve the occlusion. Good occlusion and interdigitation were obtained. Orthodontic treatment is useful for the rehabilitation of occlusal dysfunction caused by multiple maxillofacial bone fractures.

Importance of dual delivery systems for bone tissue engineering.

PubMed

Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

2016-03-10

Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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.

On the black hole lens and its foci

NASA Technical Reports Server (NTRS)

Eshleman, Von R.; Gurrola, Eric M.; Lindal, Gunnar F.

1989-01-01

Methods developed for radio occultation studies of planetary atmospheres are used to predict the electromagnetic focusing properties of a refracting lens representation of a Schwarzschild black hole. The infinity of foci are of three distinct types: a principal forward axial focus which is by far the strongest; higher-order forward axial foci; and backward conical foci with axial nulls.

Focusing light through strongly scattering media by controlling binary amplitude optimization using genetic algorithm

NASA Astrophysics Data System (ADS)

Liu, Zhipeng; Zhang, Bin; Feng, Qi; Chen, Zhaoyang; Lin, Chengyou; Ding, Yingchun

2017-06-01

Focusing light through strongly scattering media plays an important role in biomedical imaging and therapy. Here, we experimentally demonstrate light focusing through ZnO sample by controlling binary amplitude optimization using genetic algorithm. In the experiment, we use a Micro Electro-Mechanical System (MEMS)-based digital micromirror device (DMD) which is in amplitude-only modulation mode. The DMD consists of 1920×1080 square mirrors that can be independently controlled to reflect light to a desired position. We control only 160 thousand mirrors which are divided into 400 segments to modulate light focusing through the scattering media using advanced genetic algorithm. Light intensity at the target position is enhanced up to 50+/-5 times the average speckle intensity. The diameters of focusing spot can be changed ranging from 7 μm to 70 μm at arbitrary positions and multiple foci are obtained simultaneously. The spatial arrangement of multiple foci can be flexibly controlled. The advantage of DMDs lies in their switching speed up to 30 kHz, which has the potential to generate a focus in an ultra-short period of time. Our work provides a reference for the study of high speed wavefront shaping that is required in vivo tissues imaging.

Immunodetection of osteoadherin in murine tooth extracellular matrices.

PubMed

Couble, Marie-Lise; Bleicher, Françoise; Farges, Jean-Christophe; Peyrol, Simone; Lucchini, Marion; Magloire, Henry; Staquet, Marie-Jeanne

2004-01-01

An antiserum was generated from synthetic peptides highly conserved between different mammalian species to immunolocalise the small leucine-rich proteoglycan osteoadherin (OSAD) in murine teeth. In 19-day-old embryos of rats and mice, a positive staining was found in incisor predentin and alveolar bone surrounding developing incisors and molars. In newborns, OSAD was detected at the tip of the first molar cusp where it accumulated in predentin concomitantly with odontoblast differentiation. In 2-day-old rats and mice, in the first molar, immunostaining revealed positive predentin, enamel matrix close to the apical pole of ameloblasts and a strong signal in dentin. At this stage, OSAD was detected in predentin in the second molar. Ultrastructural immunocytochemistry showed gold particles associated with collagen fibres in predentin and in foci at the dentin mineralisation front. Gold particles were also detected near the secretory pole of ameloblasts where enamel crystallites elongate. No staining was detected in pulp tissue and dental follicle. Restriction of OSAD expression to the extracellular matrix of bone, dentin and enamel suggests a role of this proteoglycan in the organisation of mineralised tissues.

Generalized palisaded neutrophilic and granulomatous dermatitis-a cutaneous manifestation of chronic myelomonocytic leukemia? A clinical, histopathological, and molecular study of 3 cases.

PubMed

Federmann, Birgit; Bonzheim, Irina; Yazdi, Amir S; Schmidt, Janine; Fend, Falko; Metzler, Gisela

2017-06-01

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is characterized by erythematous papules or plaques on trunk or limbs and is frequently associated with rheumatologic, autoimmune, or hematologic malignancies. Histopathology shows interstitial granulomas composed of epitheloid histiocytes in the reticular dermis with surrounding foci of collagen degeneration and variable neutrophilic inflammation. We report 3 cases of generalized PNGD associated with chronic myelomonocytic leukemia (CMML), a myelodysplastic/myeloproliferative neoplasm, which may show a variety of cutaneous manifestations. SRSF2 P95 hotspot mutations, found in 40%-50% of CMML cases, were retrospectively detected in skin and bone marrow biopsies of all 3 patients, in 1 of them already 5 years before CMML diagnosis. Generalized PNGD may represent a type of cutaneous manifestation of CMML. Because diagnosis of CMML is frequently difficult in cases with isolated persistent monocytosis and minimal dysplasia in the bone marrow, patients with a generalized PNGD should be evaluated for the presence of hematologic disorders including CMML, ideally supported by mutational analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Sewage sludge does not induce genotoxicity and carcinogenesis.

PubMed

Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

2012-07-01

Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3(rd) week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P(+) AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group.

Bone scan as a screening test for missed fractures in severely injured patients.

PubMed

Lee, K-J; Jung, K; Kim, J; Kwon, J

2014-12-01

In many cases, patients with severe blunt trauma have multiple fractures throughout the body. These fractures are not often detectable by history or physical examination, and their diagnosis can be delayed or even missed. Thus, screening test fractures of the whole body is required after initial management. We performed this study to evaluate the reliability of bone scans for detecting missed fractures in patients with multiple severe traumas and we analyzed the causes of missed fractures by using bone scan. A bone scan is useful as a screening test for fractures of the entire body of severe trauma patients who are passed the acute phase. We reviewed the electronic medical records of severe trauma patients who underwent a bone scan from September 2009 to December 2010. Demographic and medical data were compared and statistically analyzed to determine whether missed fractures were detected after bone scan in the two groups. A total of 382 patients who had an injury severity score [ISS] greater than 16 points with multiple traumas visited the emergency room. One hundred and thirty-one patients underwent bone scan and 81 patients were identified with missed fractures by bone scan. The most frequent location for missed fractures was the rib area (55 cases, 41.98%), followed by the extremities (42 cases, 32.06%). The missed fractures that required surgery or splint were most common in extremities (11 cases). In univariate analysis, higher ISS scores and mechanism of injury were related with the probability that missed fractures would be found with a bone scan. The ISS score was statistically significant in multivariate analysis. Bone scan is an effective method of detecting missed fractures among patients with multiple severe traumas. Level IV, retrospective study. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation.

PubMed

Tripathi, Kaushlendra; Hussein, Usama K; Anupalli, Roja; Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P; Owen, Laurie B; Piazza, Gary A; Palle, Komaraiah

2015-03-10

Allyl isothiocyanate (AITC), a constituent of many cruciferous vegetables exhibits significant anticancer activities in many cancer models. Our studies provide novel insights into AITC-induced anticancer mechanisms in human A549 and H1299 non-small cell lung cancer (NSCLC) cells. AITC exposure induced replication stress in NSCLC cells as evidenced by γH2AX and FANCD2 foci, ATM/ATR-mediated checkpoint responses and S and G2/M cell cycle arrest. Furthermore, AITC-induced FANCD2 foci displayed co-localization with BrdU foci, indicating stalled or collapsed replication forks in these cells. Although PITC (phenyl isothiocyanate) exhibited concentration-dependent cytotoxic effects, treatment was less effective compared to AITC. Previously, agents that induce cell cycle arrest in S and G2/M phases were shown to sensitize tumor cells to radiation. Similar to these observations, combination therapy involving AITC followed by radiation treatment exhibited increased DDR and cell killing in NSCLC cells compared to single agent treatment. Combination index (CI) analysis revealed synergistic effects at multiple doses of AITC and radiation, resulting in CI values of less than 0.7 at Fa of 0.5 (50% reduction in survival). Collectively, these studies identify an important anticancer mechanism displayed by AITC, and suggest that the combination of AITC and radiation could be an effective therapy for NSCLC.

The 3-dimensional structure of isolated and small foci of prostatic adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

PubMed

Mai, Kien T; Burns, Bruce F; Stinson, William A; Morash, Christopher

2007-03-01

Transitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. Twelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. Eight ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. PAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.

Sensorless adaptive optics for isoSTED nanoscopy

NASA Astrophysics Data System (ADS)

Antonello, Jacopo; Hao, Xiang; Allgeyer, Edward S.; Bewersdorf, Joerg; Rittscher, Jens; Booth, Martin J.

2018-02-01

The presence of aberrations is a major concern when using fluorescence microscopy to image deep inside tissue. Aberrations due to refractive index mismatch and heterogeneity of the specimen under investigation cause severe reduction in the amount of fluorescence emission that is collected by the microscope. Furthermore, aberrations adversely affect the resolution, leading to loss of fine detail in the acquired images. These phenomena are particularly troublesome for super-resolution microscopy techniques such as isotropic stimulated-emission-depletion microscopy (isoSTED), which relies on accurate control of the shape and co-alignment of multiple excitation and depletion foci to operate as expected and to achieve the super-resolution effect. Aberrations can be suppressed by implementing sensorless adaptive optics techniques, whereby aberration correction is achieved by maximising a certain image quality metric. In confocal microscopy for example, one can employ the total image brightness as an image quality metric. Aberration correction is subsequently achieved by iteratively changing the settings of a wavefront corrector device until the metric is maximised. This simplistic approach has limited applicability to isoSTED microscopy where, due to the complex interplay between the excitation and depletion foci, maximising the total image brightness can lead to introducing aberrations in the depletion foci. In this work we first consider the effects that different aberration modes have on isoSTED microscopes. We then propose an iterative, wavelet-based aberration correction algorithm and evaluate its benefits.

Dentigenous infectious foci – a risk factor of infective endocarditis

PubMed Central

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

Quality of life in childhood epilepsy with lateralized epileptogenic foci.

PubMed

Mathiak, Krystyna A; Luba, Małgorzata; Mathiak, Klaus; Karzel, Katarzyna; Wolańczyk, Tomasz; Szczepanik, Elzbieta; Ostaszewski, Paweł

2010-08-17

Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

Quality of life in childhood epilepsy with lateralized epileptogenic foci

PubMed Central

2010-01-01

Background Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Methods Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. Results We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. Conclusions We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development. PMID:20716372

Fibre optic confocal imaging (FOCI) for subsurface microscopy of the colon in vivo.

PubMed Central

Delaney, P M; King, R G; Lambert, J R; Harris, M R

1994-01-01

Fibre optic confocal imaging (FOCI) is a new type of microscopy which has been recently developed (Delaney et al. 1993). In contrast to conventional light microscopy, FOCI and other confocal techniques allow clear imaging of subsurface structures within translucent objects. However, unlike conventional confocal microscopes which are bulky (because of a need for accurate alignment of large components) FOCI allows the imaging end to be miniaturised and relatively mobile. FOCI is thus particularly suited for clear subsurface imaging of structures within living animals or subjects. The aim of the present study was to assess the suitability of using FOCI for imaging of subsurface structures within the colon, both in vitro (human and rat biopsies) and in vivo (in rats). Images were obtained in fluorescence mode (excitation 488 nm, detection above 515 nm) following topical application of fluorescein. By this technique the glandular structure of the colon was imaged. FOCI is thus suitable for subsurface imaging of the colon in vivo. Images Fig. 2 Fig. 3 PMID:8157487

FOCIS goes south: advances in translational and clinical immunology.

PubMed

Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

2017-09-01

FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

[Effects of pamidronate disodium (Bonin) combined with chemotherapy on bone pain in multiple myeloma].

PubMed

Leng, Yun; Chen, Shi-lun; Shi, Hong-zhi

2002-10-01

Objective. To evaluate the therapeutic effects of Disodium Pamidronate (Bonin) on bone pain in multiple myeloma. Method. 18 patients received only chemotherapy and 16 patients with addition of Bonin were compared. Result. The bone pain was significantly relieved both in chemotherapy alone group and in the combination group of Bonin with chemotherapy after treatment (P<0.01, as compared with before therapy). However, the effects of combination group were more dramatical than that of the other group (P<0.05). No obvious side-effects were observed except mild fever in one patient in the combination group. Conclusion. Bonin, as a safe and effective Bisphosphonates preparation, could relieve bone pain in multiple myeloma more effectively when combined with chemotherapy.

Stochastic properties of radiation-induced DSB: DSB distributions in large scale chromatin loops, the HPRT gene and within the visible volumes of DNA repair foci.

PubMed

Ponomarev, Artem L; Costes, Sylvain V; Cucinotta, Francis A

2008-11-01

We computed probabilities to have multiple double-strand breaks (DSB), which are produced in DNA on a regional scale, and not in close vicinity, in volumes matching the size of DNA damage foci, of a large chromatin loop, and in the physical volume of DNA containing the HPRT (human hypoxanthine phosphoribosyltransferase) locus. The model is based on a Monte Carlo description of DSB formation by heavy ions in the spatial context of the entire human genome contained within the cell nucleus, as well as at the gene sequence level. We showed that a finite physical volume corresponding to a visible DNA repair focus, believed to be associated with one DSB, can contain multiple DSB due to heavy ion track structure and the DNA supercoiled topography. A corrective distribution was introduced, which was a conditional probability to have excess DSB in a focus volume, given that there was already one present. The corrective distribution was calculated for 19.5 MeV/amu N ions, 3.77 MeV/amu alpha-particles, 1000 MeV/amu Fe ions, and X-rays. The corrected initial DSB yield from the experimental data on DNA repair foci was calculated. The DSB yield based on the corrective function converts the focus yield into the DSB yield, which is comparable with the DSB yield based on the earlier PFGE experiments. The distribution of DSB within the physical limits of the HPRT gene was analyzed by a similar method as well. This corrective procedure shows the applicability of the model and empowers the researcher with a tool to better analyze focus statistics. The model enables researchers to analyze the DSB yield based on focus statistics in real experimental situations that lack one-to-one focus-to-DSB correspondance.

Cellular Mechanisms of Multiple Myeloma Bone Disease

PubMed Central

Oranger, Angela; Carbone, Claudia; Izzo, Maddalena; Grano, Maria

2013-01-01

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and decreased osteoblast differentiation. A dysregulated production of numerous cytokines that can contribute to the uncoupling of bone cell activity is well documented in the bone marrow microenvironment of MM patients. These molecules are produced not only by malignant plasma cells, that directly contribute to MM bone disease, but also by bone, immune, and stromal cells interacting with each other in the bone microenvironment. This review focuses on the current knowledge of MM bone disease biology, with particular regard on the role of bone and immune cells in producing cytokines critical for malignant plasma cell proliferation as well as in osteolysis development. Therefore, the understanding of MM pathogenesis could be useful to the discovery of novel agents that will be able to both restore bone remodelling and reduce tumor burden. PMID:23818912

Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma.

PubMed

Beuthien-Baumann, B; Strumpf, A; Zessin, J; Bredow, J; Kotzerke, J

2007-10-01

In patients with medullary thyroid carcinoma (MTC), rising levels of the tumour markers calcitonin and CEA after primary surgery indicate tumour recurrence or metastases. The only chance of cure is the resection of localised tumour tissue. For positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) and (18)F-dihydroxyphenylalanine ((18)F-DOPA), sensitivities of 78% and 63% have been reported, but in a considerable percentage of MTC patients the source of tumour marker elevation is not detected. The aim of this retrospective data evaluation was to compare the value of PET with (18)F-FDG, (18)F-DOPA and the amino acid tracer 3-O-methyl-6-[(18)F]fluoro-DOPA ((18)F-OMFD) in the detection of MTC recurrence. Fifteen patients with elevated calcitonin were investigated with PET as part of their individual clinical work-up. All patients underwent (18)F-FDG PET and (18)F-DOPA PET, and ten patients underwent (18)F-OMFD PET. With (18)F-FDG, seven patients showed foci in the neck, mediastinum, upper abdomen or bone. In seven patients, (18)F-DOPA revealed suspicious foci; five of these seven patients showed partially corresponding uptake of (18)F-FDG in the neck and mediastinum. Two of these patients underwent surgery and metastases were verified. With (18)F-OMFD, a small focus in the liver was suspected in one patient without a correlate on (18)F-FDG PET, (18)F-DOPA PET or conventional imaging. (18)F-FDG and (18)F-DOPA showed foci that were highly suspicious for local recurrence or metastasis of MTC, although histological verification in these patients with numerous previous surgical interventions was performed in only two patients. The amino acid tracer (18)F-OMFD had no diagnostic impact in these patients.

Evidence supporting pre-radiation elimination of oral foci of infection in head and neck cancer patients to prevent oral sequelae. A systematic review.

PubMed

Schuurhuis, Jennifer M; Stokman, Monique A; Witjes, Max J H; Dijkstra, Pieter U; Vissink, Arjan; Spijkervet, Frederik K L

2015-03-01

Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of pre-radiation elimination of oral foci of infection in preventing oral sequelae. A search was conducted (MEDLINE/EMBASE) for papers published up to May 2014. Papers on head-neck cancer patients subjected to pre-radiation dental screening, (chemo)radiation and oral follow-up were included. Of the 1770 identified papers, 20 studies fulfilled the inclusion criteria of which 17 were retrospective. A great heterogeneity in patient groups, dental screening techniques, definitions of oral foci of infection and techniques for eliminating foci was found. Most papers lacked essential details on how dental screening was performed and a clear definition of an oral focus of infection. The evidence for efficacy of elimination of oral foci of infection to prevent post-radiotherapy oral sequelae was inconclusive. Consequently, the efficacy of pre-radiation elimination of oral foci of infection remains unclear. No conclusions can be drawn about a definition of an oral focus of infection and whether pre-radiation elimination of these foci should be mandatory. We therefore suggest prospective studies with well-defined criteria for oral foci of infection, a clear description of which foci were eliminated and how, a detailed description of pre-radiation dental screening, clearly described patient and tumor characteristics, and a detailed dental history and dental status. Subsequently, oral problems that occur post-radiation should be systematically recorded. Copyright © 2014 Elsevier Ltd. All rights reserved.

Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7weeks of radiotherapy.

PubMed

Qvarnström, Fredrik; Simonsson, Martin; Nyman, Jan; Hermansson, Ingegerd; Book, Majlis; Johansson, Karl-Axel; Turesson, Ingela

2017-01-01

Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05-1.10Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies (n=452) were collected at 30min, and 2, 3, 24, and 72h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. HRS in keratinocytes was evidenced by the dose-response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3Gy, persistent foci could be observed even at 72h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose-response relationships. These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multiple environmental factor analysis in habitats of the harvest mite Neotrombicula autumnalis (Acari: Trombiculidae) suggests extraordinarily high euryoecious biology.

PubMed

Schöler, Arne; Maier, Walter A; Kampen, Helge

2006-01-01

The harvest mite Neotrombicula autumnalis (Trombiculidae) has become a great nuisance in various vegetated areas in Germany over the last 15 years. According to reports of dermatologists, this species appears to have propagated and spread significantly. Moreover, cases of severe trombidiosis or trombidiosis-like skin reactions have been noticed at unusually early times of the year. Due to the lack of scientific studies, little is known about the ecology of N. autumnalis and its distribution, and preferred habitats cannot be predicted. A four-year study was conducted to identify trombiculid foci in different areas of Bonn in order (1) to determine the timing of larvae appearance in different years, (2) to identify the factors that lead to high larvae abundances at the mite foci ('multiple factor analysis'), and (3) to develop an ecological control strategy. By means of the 'tile catch method' (TCM) which turned out to be most appropriate to collect data on the distribution and abundances of trombiculid mites, larvae of N. autumnalis were caught from mid July until the end of October/beginning of November. The distribution of the mites was patchy, supporting the hypothesis that certain factors cause a concentration in foci. Most of the mite foci had a fixed location for at least three years. Efforts to isolate nymphs and adults in larger quantities to gain knowledge about their preferred soil areas and soil depths failed. Only some nymphs of N. autumnalis could be found living 10-40 cm deep in the soil. Due to the restriction that the nymphs and adults can only rarely be isolated in the ground, the analysis of environmental factors was executed based on abundances of questing larvae on the soil surface. The detailed analysis of soil-physical, soil-chemical and meso-faunistic factors could not finally explain the unequal distribution of the mites, although the porosity of the soil had a statistically significant slight influence on the abundance of larvae, and soil pH bordered significance, also suggesting a slight influence. Furthermore, soil temperatures during the winter seasons in three subsequent years appeared too high to affect the harvest mite. The field experiments suggest that N. autumnalis and particularly its larval stages are extremely euryoecious (meaning tolerating very different environmental conditions). Further studies are necessary: additional investigations on the influence of certain abiotic environmental factors on N. autumnalis, the search for factors underlying the rhythmicity of its life cycle ('zeitgeber'), and the reasons and mechanisms for heterogeneous distribution of soil fauna in general. Ecological control of the mite is, in principle, possible but only after identifying the foci and ascertaining their approximate dimensions with the TCM. This control strategy is the most promising one, albeit very laborious, emphasising the need of further research on the ecology of the harvest mite.

Multiscale imaging of bone microdamage

PubMed Central

Poundarik, Atharva A.; Vashishth, Deepak

2015-01-01

Bone is a structural and hierarchical composite that exhibits remarkable ability to sustain complex mechanical loading and resist fracture. Bone quality encompasses various attributes of bone matrix from the quality of its material components (type-I collagen, mineral and non-collagenous matrix proteins) and cancellous microarchitecture, to the nature and extent of bone microdamage. Microdamage, produced during loading, manifests in multiple forms across the scales of hierarchy in bone and functions to dissipate energy and avert fracture. Microdamage formation is a key determinant of bone quality, and through a range of biological and physical mechanisms, accumulates with age and disease. Accumulated microdamage in bone decreases bone strength and increases bone’s propensity to fracture. Thus, a thorough assessment of microdamage, across the hierarchical levels of bone, is crucial to better understand bone quality and bone fracture. This review article details multiple imaging modalities that have been used to study and characterize microdamage; from bulk staining techniques originally developed by Harold Frost to assess linear microcracks, to atomic force microscopy, a modality that revealed mechanistic insights into the formation diffuse damage at the ultrastructural level in bone. New automated techniques using imaging modalities such as microcomputed tomography are also presented for a comprehensive overview. PMID:25664772

Regulation of Fanconi anemia protein FANCD2 monoubiquitination by miR-302

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

Suresh, Bharathi; College of Medicine, Hanyang University, Seoul; Kumar, A. Madhan

2015-10-16

Fanconi anemia (FA) is a recessively inherited multigene disease characterized by congenital defects, progressive bone marrow failure, and heightened cancer susceptibility. Monoubiquitination of the FA pathway member FANCD2 contributes to the repair of replication stalling DNA lesions. However, cellular regulation of FANCD2 monoubiquitination remains poorly understood. In the present study, we identified the miR-302 cluster as a potential regulator of FANCD2 by bioinformatics analysis. MicroRNAs (miRNAs) are the major posttranscriptional regulators of a wide variety of biological processes, and have been implicated in a number of diseases. Expression of the exogenous miR-302 cluster (without miR-367) reduced FANCD2 monoubiquitination and nuclearmore » foci formation. Furthermore, miR-302 cells showed extensive chromosomal breakage upon MMC treatment when compared to mock control cells. Taken together, our results suggest that overexpression of miR-302 plays a critical role in the regulation of FANCD2 monoubiquitination, resulting in characteristic defects in DNA repair within cells. - Highlights: • miR-302 binds to the 3′UTR promoter of the FANCD2 gene to regulate gene expression. • miR-302 cluster down-regulates FANCD2 protein expression. • miR-302 cluster reduces FANCD2 monoubiquitination and nuclear foci formation. • miR-302 exhibits the characteristic defects in DNA repair in cells.« less

Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report.

PubMed

Hara, Hitomi; Kawamoto, Teruya; Onishi, Yasuo; Fujioka, Hiroyuki; Nishida, Kotaro; Kuroda, Ryosuke; Kurosaka, Masahiro; Akisue, Toshihiro

2016-01-01

We report the case of a 32-year-old Japanese female with a giant cell tumor of bone involving multiple midfoot bones. Giant cell tumors of bone account for approximately 5% of all primary bone tumors and most often arise at the ends of long bones. The small bones, such as those of the hands and feet, are rare sites for giant cell tumors. Giant cell tumors of the small bones tend to exhibit more aggressive clinical behavior than those of the long bones. The present patient underwent en bloc tumor excision involving multiple tarsals and metatarsals. We reconstructed the longitudinal arch of the foot with a free vascularized fibular graft. At the 2-year follow-up visit, bony union had been achieved, with no tumor recurrence. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Recurrent mycobacterial osteomyelitis. Report of a case due to Mycobacterium avium-intracellulare-scrofulaceum complex and BCG vaccination.

PubMed

Solheim, L F; Kjelsberg, F

1982-01-01

A 28-year-old man suffering from recurrent mycobacterial osteomyelitis during several years is reported. Eight years old he had a Mycobacterium scrofulaceum infection in his right calcaneus. A serious infection with multiple foci of osteomyelitis occurred after BCG vaccination at the age of 14 years and 11 years later multifocal lesions of osteomyelitis due to Mycobacterium avium-intracellulare-scrofulaceum complex appeared. The special clinical problems due to the relative or complete resistence of these organisms to antituberculous drugs are emphasized. The mainstays of treatment are surgical revision and drainage with prolonged and intensive multiple drug therapy.

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

PubMed Central

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 of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. Methods: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. Results: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. Conclusions: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy. PMID:27002936

A "reverse" Maffucci's syndrome: case report and short review of the literature.

PubMed

Matzaroglou, Charalampos; Megas, Panagiotis; Panagiotopoulos, Elias; Notopoulos, Athanasios; Saridis, Alkis; Sourgiadaki, Efrosini; Koumoundourou, Dimitra; Dimakopoulos, Panagiotis

2005-01-01

Maffucci's syndrome is a congenital, non-hereditary mesodermal dysplasia associated with multiple enchondromas and after some years accompanied by hemangiomas. We describe a rare case of "reverse" Maffucci's syndrome in a 42-year-old woman who has suffered from multiple hemangiomas for the last 24 years. The last two years she complained for heel pain. Bone scintigraphic examination showed abnormal findings in the left calcaneal bone. The scintigraphy, radiology and histology findings revealed multiple enchondromas, so the diagnosis was changed into Maffucci's syndrome. After one year, the left calcaneal bone showed sarcomatous transformation.

Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition.

PubMed

Matsumoto, Hotaru; Saitoh, Hisato

2016-07-29

We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. Copyright © 2016 Elsevier Inc. All rights reserved.

Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.

PubMed

Hu, Jiaxin; Rong, Ziye; Gong, Xin; Zhou, Zhengyang; Sharma, Vivek K; Xing, Chao; Watts, Jonathan K; Corey, David R; Mootha, V Vinod

2018-03-15

Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

PubMed Central

Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

2013-01-01

Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance. PMID:22773604

Theoretical and experimental investigation of multispectral photoacoustic osteoporosis detection method

NASA Astrophysics Data System (ADS)

Steinberg, Idan; Hershkovich, Hadas Sara; Gannot, Israel; Eyal, Avishay

2014-03-01

Osteoporosis is a widespread disorder, which has a catastrophic impact on patients lives and overwhelming related to healthcare costs. Recently, we proposed a multispectral photoacoustic technique for early detection of osteoporosis. Such technique has great advantages over pure ultrasonic or optical methods as it allows the deduction of both bone functionality from the bone absorption spectrum and bone resistance to fracture from the characteristics of the ultrasound propagation. We demonstrated the propagation of multiple acoustic modes in animal bones in-vitro. To further investigate the effects of multiple wavelength excitations and of induced osteoporosis on the PA signal a multispectral photoacoustic system is presented. The experimental investigation is based on measuring the interference of multiple acoustic modes. The performance of the system is evaluated and a simple two mode theoretical model is fitted to the measured phase signals. The results show that such PA technique is accurate and repeatable. Then a multiple wavelength excitation is tested. It is shown that the PA response due to different excitation wavelengths revels that absorption by the different bone constitutes has a profound effect on the mode generation. The PA response is measured in single wavelength before and after induced osteoporosis. Results show that induced osteoporosis alters the measured amplitude and phase in a consistent manner which allows the detection of the onset of osteoporosis. These results suggest that a complete characterization of the bone over a region of both acoustic and optical frequencies might be used as a powerful tool for in-vivo bone evaluation.

Extending Rest between Unloading Cycles Does Not Enhance Bone's Long-Term Recovery.

PubMed

Manske, Sarah L; Vijayaraghavan, Surabhi; Tuthill, Alyssa; Brutus, Olivier; Yang, Jie; Gupta, Shikha; Judex, Stefan

2015-10-01

Multiple exposures to unloading are overall more deleterious to the skeleton than is single exposure, although the rate of bone loss may diminish during multiple exposures. Here, we determined whether extending the reambulation (RA) period from 3 wk to 9 wk will mitigate bone loss during three distinct 3-wk hindlimb unloading (HLU) periods and enhance long-term recovery in skeletally mature, genetically heterogeneous mice. Female adult mice (4 months old) were subjected to three cycles of 3-wk unloading with 3-wk or 9-wk RA periods in between. Mice were terminated 46 wk after initiation of the study. Outcome measures for the distal femur were determined from multiple in vivo micro-computed tomography scans and finite-element modeling. Tripling RA duration enhanced trabecular bone recovery in between HLU periods but also increased the rate of loss of bone volume fraction (bone volume/tissue volume) and metaphyseal stiffness during subsequent HLU periods. With shorter RA periods, the magnitude of bone loss decreased by the second HLU period, whereas this decrease was delayed with longer RA periods. RA duration did not affect long-term recovery 46 wk after the start of the experimental protocol, as both HLU groups had similar levels of bone volume/tissue volume, cortical area, and stiffness. Individual cage activity levels were unrelated to the magnitude of bone loss during HLU or bone recovery during RA. These data suggest that extending recovery duration between periods of unloading may provide temporary benefits but is an ineffective long-term strategy for combating the devastation of trabecular morphology and mechanics, as temporarily enhanced recovery is largely cancelled out by greater susceptibility to unloading. They also emphasize that cortical bone is more amenable to long-term recovery than is trabecular bone.

Bone x-ray

MedlinePlus

... different views of the bone may be uncomfortable. Why the Test is Performed A bone x-ray ... neoplasia (MEN) II Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Paget's disease Primary hyperparathyroidism Rickets Risks There ...

Apo2L/TRAIL Inhibits Tumor Growth and Bone Destruction in a Murine Model of Multiple Myeloma

PubMed Central

Labrinidis, Agatha; Diamond, Peter; Martin, Sally; Hay, Shelley; Liapis, Vasilios; Zinonos, Irene; Sims, Natalie A.; Atkins, Gerald J.; Vincent, Cristina; Ponomarev, Vladimir; Findlay, David M.; Zannettino, Andrew C.W.; Evdokiou, Andreas

2017-01-01

Purpose Multiple myeloma is an incurable disease, for which the development of new therapeutic approaches is required. Here, we report on the efficacy of recombinant soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to inhibit tumor progression and bone destruction in a xenogeneic model of human multiple myeloma. Experimental Design We established a mouse model of myeloma, in which Apo2L/TRAIL-sensitive RPMI-8226 or KMS-11 cells, tagged with a triple reporter gene construct (NES-HSV-TK/GFP/Luc), were transplanted directly into the tibial marrow cavity of nude mice. Tumor burden was monitored progressively by bioluminescence imaging and the development of myeloma-induced osteolysis was measured using high resolution in vivo micro-computed tomography. Results Tumor burden increased progressively in the tibial marrow cavity of mice transplanted with Apo2L/TRAIL-sensitive RPMI-8226 or KMS-11 cells associated with extensive osteolysis directly in the area of cancer cell transplantation. Treatment of mice with recombinant soluble Apo2L/TRAIL reduced myeloma burden in the bone marrow cavity and significantly protected against myeloma-induced osteolysis. The protective effects of Apo2L/TRAIL treatment on bone were mediated by the direct apoptotic actions of Apo2L/TRAIL on myeloma cells within the bone microenvironment. Conclusions This is the first in vivo study that investigates the efficacy of recombinant Apo2L/TRAIL on myeloma burden within the bone microenvironment and associated myeloma-induced bone destruction. Our findings that recombinant soluble Apo2L/TRAIL reduces myeloma burden within the bone microenvironment and protects the bone from myeloma-induced bone destruction argue against an inhibitory role of osteoprotegerin in Apo2L/TRAIL-induced apoptosis in vivo and highlight the need to clinically evaluate Apo2L/TRAIL in patients with multiple myeloma. PMID:19276263

Subnuclear foci quantification using high-throughput 3D image cytometry

NASA Astrophysics Data System (ADS)

Wadduwage, Dushan N.; Parrish, Marcus; Choi, Heejin; Engelward, Bevin P.; Matsudaira, Paul; So, Peter T. C.

2015-07-01

Ionising radiation causes various types of DNA damages including double strand breaks (DSBs). DSBs are often recognized by DNA repair protein ATM which forms gamma-H2AX foci at the site of the DSBs that can be visualized using immunohistochemistry. However most of such experiments are of low throughput in terms of imaging and image analysis techniques. Most of the studies still use manual counting or classification. Hence they are limited to counting a low number of foci per cell (5 foci per nucleus) as the quantification process is extremely labour intensive. Therefore we have developed a high throughput instrumentation and computational pipeline specialized for gamma-H2AX foci quantification. A population of cells with highly clustered foci inside nuclei were imaged, in 3D with submicron resolution, using an in-house developed high throughput image cytometer. Imaging speeds as high as 800 cells/second in 3D were achieved by using HiLo wide-field depth resolved imaging and a remote z-scanning technique. Then the number of foci per cell nucleus were quantified using a 3D extended maxima transform based algorithm. Our results suggests that while most of the other 2D imaging and manual quantification studies can count only up to about 5 foci per nucleus our method is capable of counting more than 100. Moreover we show that 3D analysis is significantly superior compared to the 2D techniques.

Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci.

PubMed

Mathes, Rachel L; Burdette, Erin L; Moore, Phillip A; Myrna, Kathern E

2012-03-01

To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow-up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi-squared analysis. Age and length of follow-up time were compared using a student's t-test. Ninety-one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty-eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU. © 2011 American College of Veterinary Ophthalmologists.

[Multiple myeloma with significant multifocal osteolysis in a dog without a detectible gammopathy].

PubMed

Souchon, F; Koch, A; Sohns, A

2013-01-01

Description of a variant of multiple myeloma in a dog lacking the gammopathy normally associated with this type of neoplasm. A Border Collie mongrel was presented with symptoms of progressive hind-leg weakness, lethargy and tiredness, which had started to appear 6 weeks previously. Radiographic examination showed small osteolytic areas in the spinal column, but also diffuse small areas of increased opacity as well as evidence of decreased bone density in the pelvis and of both femoral necks. Moderate regenerative anaemia, hypogammopathy and hypercalcaemia were diagnosed. Computed tomography scans displayed multifocal osteolysis and bone destruction in the skull, spinal column, scapulae, proximal humeri, pelvis and femoral necks. H&E staining of the biopsies showed bone destruction and monomorphic plasmacyotid cell populations, causing infiltrative bone marrow lesions and osteolysis. In many areas neoplastic plasma cell infiltration of the bone marrow was 70% and in some areas reached 100%. The diagnosis was non-secretory multiple myeloma without apparent secretion of paraproteins into the blood.

A Cajal body-independent pathway for telomerase trafficking in mice

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

Tomlinson, Rebecca L.; Li, Jian; Culp, Bradley R.

2010-10-15

The intranuclear trafficking of human telomerase involves a dynamic interplay between multiple nuclear sites, most notably Cajal bodies and telomeres. Cajal bodies are proposed to serve as sites of telomerase maturation, storage, and assembly, as well as to function in the cell cycle-regulated delivery of telomerase to telomeres in human cells. Here, we find that telomerase RNA does not localize to Cajal bodies in mouse cells, and instead resides in separate nuclear foci throughout much of the cell cycle. However, as in humans, mouse telomerase RNA (mTR) localizes to subsets of telomeres specifically during S phase. The localization of mTRmore » to telomeres in mouse cells does not require coilin-containing Cajal bodies, as mTR is found at telomeres at similar frequencies in cells from wild-type and coilin knockout mice. At the same time, we find that human TR localizes to Cajal bodies (as well as telomeres) in mouse cells, indicating that the distinct trafficking of mTR is attributable to an intrinsic property of the RNA (rather than a difference in the mouse cell environment such as the properties of mouse Cajal bodies). We also find that during S phase, mTR foci coalesce into short chains, with at least one of the conjoined mTR foci co-localizing with a telomere. These findings point to a novel, Cajal body-independent pathway for telomerase biogenesis and trafficking in mice.« less

Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs

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

Guilloteau, L.; Pepin, M.; Pardon, P.

1990-10-01

The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored (1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and (2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteriamore » into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process.« less

γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.

PubMed

Yashavarddhan, M H; Shukla, Sandeep K; Srivastava, Nitya N; Suar, Mrutyunjay; Dutta, Sangeeta; Kalita, Bhargab; Ranjan, Rajiv; Singh, Abhinav; Bajaj, Sania; Gupta, Manju L

2016-07-01

DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Brain Proteome of the Ubiquitin Ligase Peli1 Knock-Out Mouse during Experimental Autoimmune Encephalomyelitis.

PubMed

Lereim, Ragnhild Reehorst; Oveland, Eystein; Xiao, Yichuan; Torkildsen, Øivind; Wergeland, Stig; Myhr, Kjell-Morten; Sun, Shao-Cong; Berven, Frode S

2016-09-01

The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak. Brain samples from the frontal hemisphere, peripheral from the extensive inflammatory foci, were analyzed using TMT-labeling of sample pools, and the discovered proteins were verified in individual mice using label-free proteomics. The greatest proteomic differences between Peli1 knock-out and wild-type mice were observed at the disease peak. In Peli1 knock-out a higher degree of antigen presentation, increased activity of adaptive and innate immune cells and alterations to proteins involved in iron metabolism were observed during experimental autoimmune encephalomyelitis. These results unravel global effects to the brain proteome when abrogating Peli1 expression, underlining the importance of Peli1 as a regulator of the immune response also peripheral to inflammatory foci during experimental autoimmune encephalomyelitis. The proteomics data is available in PRIDE with accession PXD003710.

RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

PubMed Central

Watson, Nicholas B.; Nelson, Eric; Digman, Michelle; Thornburg, Joshua A.; Alphenaar, Bruce W.; McGregor, W. Glenn

2008-01-01

Proteins required for translesion DNA synthesis localize in nuclear foci of cells with replication-blocking lesions. The dynamics of this process were examined in human cells with fluorescence-based biophysical techniques. Photobleaching recovery and raster image correlation spectroscopy experiments indicated that involvement in the nuclear foci reduced the movement of RAD18 from diffusion-controlled to virtual immobility. Examination of the mobility of REV1 indicated that it is similarly immobilized when it is observed in nuclear foci. Reducing the level of RAD18 greatly reduced the focal accumulation of REV1 and reduced UV mutagenesis to background frequencies. Fluorescence lifetime measurements indicated that RAD18 and RAD6A or polη only transferred resonance energy when these proteins colocalized in damage-induced nuclear foci, indicating a close physical association only within such foci. Our data support a model in which RAD18 within damage-induced nuclear foci is immobilized and is required for recruitment of Y-family DNA polymerases and subsequent mutagenesis. In the absence of damage these proteins are not physically associated within the nucleoplasm. PMID:18926833

Objective scoring of transformed foci in BALB/c 3T3 cell transformation assay by statistical image descriptors.

PubMed

Urani, C; Corvi, R; Callegaro, G; Stefanini, F M

2013-09-01

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 adoption of the assay partially depend on a fair degree of subjectivity in foci scoring. An objective evaluation may be obtained after separating foci from background monolayer in the digital image, and quantifying values of statistical descriptors which are selected to capture eye-scored morphological features. The aim of this study was to develop statistical descriptors to be applied to transformed foci of BALB/c 3T3, which cover foci size, multilayering and invasive cell growth into the background monolayer. Proposed descriptors were applied to a database of 407 foci images to explore the numerical features, and to illustrate open problems and potential solutions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma

PubMed Central

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P. Leif; Camaschella, Clara; Campanella, Alessandro

2015-01-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. PMID:25715406

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma.

PubMed

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P Leif; Camaschella, Clara; Campanella, Alessandro

2015-06-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. Copyright© Ferrata Storti Foundation.

A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer.

PubMed

Body, Jean-Jacques; Facon, Thierry; Coleman, Robert E; Lipton, Allan; Geurs, Filip; Fan, Michelle; Holloway, Donna; Peterson, Mark C; Bekker, Pirow J

2006-02-15

Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.

Current practice of antibiotic prophylaxis for surgical fixation of closed long bone fractures: a survey of 297 members of the Orthopaedic Trauma Association.

PubMed

Gans, Itai; Jain, Amit; Sirisreetreerux, Norachart; Haut, Elliott R; Hasenboehler, Erik A

2017-01-01

The risk of postoperative surgical site infection after long bone fracture fixation can be decreased with appropriate antibiotic use. However, there is no agreement on the superiority of a single- or multiple-dose perioperative regimen of antibiotic prophylaxis. The purpose of this study is to determine the following: 1) What are the current practice patterns of orthopaedic trauma surgeons in using perioperative antibiotics for closed long bone fractures? 2) What is the current knowledge of published antibiotic prophylaxis guidelines among orthopaedic trauma surgeons? 3) Are orthopaedic surgeons willing to change their current practices? A questionnaire was distributed via email between September and December 2015 to 955 Orthopaedic Trauma Association members, of whom 297 (31%) responded. Most surgeons (96%) use cefazolin as first-line infection prophylaxis. Fifty-nine percent used a multiple-dose antibiotic regimen, 39% used a single-dose regimen, and 2% varied this decision according to patient factors. Thirty-six percent said they were unfamiliar with Centers for Disease Control and Prevention (CDC) antibiotic prophylaxis guidelines; only 30% were able to select the correct CDC recommendation from a multiple-choice list. However, 44% of surgeons said they followed CDC recommendations. Fifty-six percent answered that a single-dose antibiotic prophylaxis regimen was not inferior to a multiple-dose regimen. If a level-I study comparing a single preoperative dose versus multiple perioperative antibiotic dosing regimen for treatment of closed long bone fractures were published, most respondents (64%) said they would fully follow these guidelines, and 22% said they would partially change their practice to follow these guidelines. There is heterogeneity in the use of single- versus multiple-dose antibiotic prophylaxis for surgical repair of closed long bone fractures. Many surgeons were unsure of current evidence-based recommendations regarding perioperative antibiotic use. Most respondents indicated they would be receptive to high-level evidence regarding the single- versus multiple-dose perioperative prophylactic antibiotics for the treatment of closed long bone fractures.

Optimization of multiple quality characteristics in bone drilling using grey relational analysis

PubMed Central

Pandey, Rupesh Kumar; Panda, Sudhansu Sekhar

2014-01-01

Purpose Drilling of bone is common during bone fracture treatment to fix the fractured parts with screws wires or plates. Minimally invasive drilling of the bone has a great demand as it helps in better fixation and quick healing of the broken bones. The purpose of the present investigation is to determine the optimum cutting condition for the minimization of the temperature, force and surface roughness simultaneously during bone drilling. Method In this study, drilling experiments have been performed on bovine bone with different conditions of feed rate and drill rotational speed using full factorial design. Optimal level of the drilling parameters is determined by the grey relational grade (GRG) obtained from the GRA as the performance index of multiple quality characteristics. The effect of each drilling parameter on GRG is determined using analysis of variance (ANOVA) and the results obtained are validated by confirmation experiment. Results Grey relational analysis showed that the investigation with feed rate of 40 mm/min and spindle speed of 500 rpm has the highest grey relational grade and is recommended setting for minimum temperature, force and surface roughness simultaneously during bone drilling. Feed rate has the highest contribution (59.49%) on the multiple performance characteristics followed by the spindle speed (37.69%) as obtained from ANOVA analysis. Conclusions The use of grey relational analysis will simplify the complex process of optimization of the multi response characteristics in bone drilling by converting them into a single grey relational grade. The use of the above suggested methodology can greatly minimize the bone tissue injury during drilling. PMID:25829751

Optimization of multiple quality characteristics in bone drilling using grey relational analysis.

PubMed

Pandey, Rupesh Kumar; Panda, Sudhansu Sekhar

2015-03-01

Drilling of bone is common during bone fracture treatment to fix the fractured parts with screws wires or plates. Minimally invasive drilling of the bone has a great demand as it helps in better fixation and quick healing of the broken bones. The purpose of the present investigation is to determine the optimum cutting condition for the minimization of the temperature, force and surface roughness simultaneously during bone drilling. In this study, drilling experiments have been performed on bovine bone with different conditions of feed rate and drill rotational speed using full factorial design. Optimal level of the drilling parameters is determined by the grey relational grade (GRG) obtained from the GRA as the performance index of multiple quality characteristics. The effect of each drilling parameter on GRG is determined using analysis of variance (ANOVA) and the results obtained are validated by confirmation experiment. Grey relational analysis showed that the investigation with feed rate of 40 mm/min and spindle speed of 500 rpm has the highest grey relational grade and is recommended setting for minimum temperature, force and surface roughness simultaneously during bone drilling. Feed rate has the highest contribution (59.49%) on the multiple performance characteristics followed by the spindle speed (37.69%) as obtained from ANOVA analysis. The use of grey relational analysis will simplify the complex process of optimization of the multi response characteristics in bone drilling by converting them into a single grey relational grade. The use of the above suggested methodology can greatly minimize the bone tissue injury during drilling.

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

PubMed

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 <0.05 were considered significant. 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. 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.

UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, γ-H2AX formation, and Mre11 relocalization

PubMed Central

Limoli, Charles L.; Giedzinski, Erich; Bonner, William M.; Cleaver, James E.

2002-01-01

UV-induced replication arrest in the xeroderma pigmentosum variant (XPV) but not in normal cells leads to an accumulation of the Mre11/Rad50/Nbs1 complex and phosphorylated histone H2AX (γ-H2AX) in large nuclear foci at sites of stalled replication forks. These complexes have been shown to signal the presence of DNA damage, in particular, double-strand breaks (DSBs). This finding suggests that UV damage leads to the formation of DSBs during the course of replication arrest. After UV irradiation, XPV cells showed a fluence-dependent increase in the yield of γ-H2AX foci that paralleled the production of Mre11 foci. The percentage of foci-positive cells increased rapidly (10–15%) up to fluences of 10 J⋅m−2 before saturating at higher fluences. Frequencies of γ-H2AX and Mre11 foci both reached maxima at 4 h after UV irradiation. This pattern contrasts sharply to the situation observed after x-irradiation, where peak levels of γ-H2AX foci were found to precede the formation of Mre11 foci by several hours. The nuclear distributions of γ-H2AX and Mre11 were found to colocalize spatially after UV- but not x-irradiation. UV-irradiated XPV cells showed a one-to-one correspondence between Mre11 and γ-H2AX foci-positive cells. These results show that XPV cells develop DNA DSBs during the course of UV-induced replication arrest. These UV-induced foci occur in cells that are unable to carry out efficient bypass replication of UV damage and may contribute to further genetic variation. PMID:11756691

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review.

PubMed

Díaz-Delgado, Josué; Pool, Roy; Hoppes, Sharman; Cerezo, Argine; Quesada-Canales, Óscar; Stoica, George

2017-05-18

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

A Case of Tuberous Sclerosis Without Multiorgan Involvement.

PubMed

Falsafi, Parisa; Taghavi-Zenouz, Ali; Khorshidi-Khiyavi, Reza; Nezami, Nariman; Estiar, Mehrdad Asghari

2015-02-24

Tuberous sclerosis or Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant and progressive neurocutaneous disorder involves multiple organs mainly brain, heart, kidney, lung, liver, skin and eye. The diagnosis is typically made clinically. Here, we are reporting a case of TSC presented mainly with dermatologic findings and only neurologic manifestations on MRI. A 15-year-old female with intellectual disability is followed up at neurology clinic for history of seizure. Intelligence evaluation showed that she has intellectual disability. She had wart like lesions distributed in form of butterfly over the face especially involving nose. She did not have any sign and symptom of heart, kidney, lung, bone and eye involvement. Also, her laboratory tests were normal. Despite the physical examination showed absolutely intact neurologic examination, but brain MRI and CT scan revealed several cortical and subcortical tubers, and subependymal glial nodules; no evidence of giant cell astrocytomas and aneurysm. Hypesignal foci are seen at subcortical white matter on long TR images. Fibers are involved. In this case, there is no evidence of giant cell astrocytomas and aneurysm. It seems that TSC could be the prevalent disorder and referring intellectual disability patients in birth with normal organs could be diagnosed as TSC. Therefore, there is necessary need to design genetic natal and post natal tests for diagnosis of TSC cases. Also, there is pivotal that similar cases must be reported; perhaps TSC is more prevalent than to be considered.

Multimodal registration of three-dimensional maxillodental cone beam CT and photogrammetry data over time.

PubMed

Bolandzadeh, N; Bischof, W; Flores-Mir, C; Boulanger, P

2013-01-01

In recent years, one of the foci of orthodontics has been on systems for the evaluation of treatment results and the tracking of tissue variations over time. This can be accomplished through analysing three-dimensional orthodontic images obtained before and after the treatments. Since complementary information is achieved by integrating multiple imaging modalities, cone beam CT (CBCT) and stereophotogrammetry technologies are used in this study to develop a method for tracking bone, teeth and facial soft-tissue variations over time. We propose a two-phase procedure of multimodal (Phase 1) and multitemporal (Phase 2) registration which aligns images taken from the same patient by different imaging modalities and at different times. Extrinsic (for Phase 1) and intrinsic (for Phase 2) landmark-based registration methods are employed as an initiation for a robust iterative closest points algorithm. Since the mandible moves independently of the upper skull, the registration procedure is applied separately on the mandible and the upper skull. The results show that the signed error distributions of both mandible and skull registrations follow a mixture of two Gaussian distributions, corresponding to alignment errors (due to our method) and temporal change over time. We suggest that the large values among the total registration errors correspond to the temporal change resulting from (1) the effect of treatment (i.e. the orthodontic changes of teeth positions); (2) the biological changes such as teeth growth over time, especially for teenagers; and (3) the segmentation procedure and CBCT precision change over time.

Occipital Condyle Syndrome as an Initial Presentation of Lung Cancer: A Case Report.

PubMed

Liu, Meng-Ta; Lin, Guan-Yu; Lin, Chun-Chieh; Cheng, Chun-An; Chen, Ming-Hua; Lee, Jiunn-Tay

2015-03-01

Occipital condyle syndrome (OCS) is a rare cause of headache. This study herein reports a case in which a unique headache and tongue deviation appear as symptoms of the first presentation of a malignant tumor. A healthy 67-year-old male presented with a unilateral shooting pain in the occipital region, accompanied by slurred speech and difficulty swallowing. Neurological examinations later revealed atrophy and mild fasciculation of the tongue. The clinical symptoms and MRI results suggested OCS. Screening for tumor markers showed an elevated CEA. The chest CT revealed a lobulated soft-tissue mass in the lower left lobe, and a CTguided biopsy confirmed the diagnosis of adenocarcinoma. A whole body bone scan found multiple foci. The adenocarcinoma was graded pT2bN3M1b, stage IV. The headache improved with a prescription of prednisone, 60 mg to be taken daily. With three months of treatment, clinical examinations showed that the patient was free of pain and that there had been no progression of the atrophy or deviation of the tongue. The possible etiology of OCS includes a primary tumor or metastatic lesion that directly invades the base of the skull. Determining the underlying causes of OCS can be challenging, but MR imaging is currently the diagnostic tool of choice. An awareness of the features of OCS in healthy adults may be able to lead to earlier diagnosis of the underlying etiology and efficient relief of the symptoms.

Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

PubMed

Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

2010-09-01

Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

Heterogeneity of DNA methylation in multifocal prostate cancer.

PubMed

Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

2015-01-01

Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster analysis revealed a divergent methylation profile of paired PCa foci, while the foci from separate cases with biochemical recurrence showed similar methylation profile and the highest mean levels of DNA methylation. Our findings suggest that PCa tissue is heterogeneous, as between paired foci differences in DNA methylation status were found. Common epigenetic profile of recurrent tumors can be inferred from our data.

[Adjuvant cryosurgery in the treatment of unicameral bone cysts].

PubMed

Tena-Sanabria, Mario Edgar; Hernández-Hernández, Melissa Jesús; Tena-González, Mario Edgar; Mejía-Aranguré, Juan Manuel

2014-01-01

Multiple treatments have been used for the unicameral bone cyst lesion, such as steroid application, multiple perforations, bone curettages, partial resection and bone grafting. The purpose of this study was to describe the evolution of children with unicameral bone cyst who were treated with cryosurgery as coadjuvant therapy. Cross-sectional descriptive study over the period between January 2001 and December 2006. Twelve patients were studied and treated at the Pediatric Orthopedics Department of the Pediatrics Hospital at the Centro Médico Nacional Siglo XXI. Twelve patients were analyzed; all of them were treated with curettage, cryotherapy and bone grafting. In 7 patients, the lesions were located in the humerus (58.3 %), in 3 in the tibia (25 %), in 1 in the ilio-ischiopubic branch (8.3 %), and in 1 in the clavicle (8.3 %). Follow-up ranged from 12 to 36 months. Bone healing required 2 to 3 months after the surgery; the response was complete in 9 (75 %) patients and partial in 3 (25 %). Function was restored in all cases, without recurrences. Cryosurgery as an adjuvant treatment and autologous or homologous bone grafting prevented local recurrence of unicameral bone cyst lesions, favored bone healing and allowed for a full range of motion functionality without complications.

Multiple myeloma: diagnosis and treatment.

PubMed

Nau, Konrad C; Lewis, William D

2008-10-01

Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections, patients require broad-spectrum antibiotics for febrile illness and immunization against influenza, pneumococcus, and Haemophilus influenzae B. Five-year survival rates approach 33 percent, and the median survival rate is 33 months.

Sewage sludge does not induce genotoxicity and carcinogenesis

PubMed Central

Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

2012-01-01

Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group. PMID:23055806

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

PubMed Central

Nguyen, Lonnissa H.; Annabi, Nasim; Nikkhah, Mehdi; Bae, Hojae; Binan, Loïc; Park, Sangwon; Kang, Yunqing

2012-01-01

Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes. PMID:22765012

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

PubMed Central

Mohanty, Sindhu T.; Seckinger, Anja; Terry, Rachael L.; Pettitt, Jessica A.; Simic, Marija K.; Le, Lawrence M. T.; Kramer, Ina; Falank, Carolyne; Fairfield, Heather; Ghobrial, Irene M.; Baldock, Paul A.; Little, David G.; Kneissel, Michaela; Vanderkerken, Karin; Bassett, J. H. Duncan; Williams, Graham R.; Oyajobi, Babatunde O.; Hose, Dirk

2017-01-01

Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM. PMID:28515094

L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer

PubMed Central

Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

2016-01-01

Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

Solid variant of aneurysmal bone cyst of the thoracic spine: a case report

PubMed Central

2011-01-01

Introduction The solid variant of aneurysmal bone cyst is rare, and only 13 cases involving the spine have been reported to date, including seven in the thoracic vertebrae. The diagnosis is difficult to secure radiographically before biopsy or surgery. Case report An 18-year-old Hispanic man presented to our facility with a one-year history of left chest pain without any significant neurological deficits. An MRI scan demonstrated a 6 cm diameter enhancing multi-cystic mass centered at the T6 vertebral body with involvement of the left proximal sixth rib and extension into the pleural cavity; the spinal cord was severely compressed with evidence of abnormal T2 signal changes. Our patient was taken to the operating room for a total spondylectomy of T6 with resection of the left sixth rib from a single-stage posterior-only approach. The vertebral column was reconstructed in a 360° manner with an expandable titanium cage and pedicle screw fixation. Histologically, the resected specimen showed predominant solid fibroblastic proliferation, with minor foci of reactive osteoid formation, an area of osteoclastic-like giant cells, and cyst-like areas filled with erythrocytes and focal hemorrhage, consistent with a predominantly solid variant of aneurysmal bone cyst. At 16 months after surgery, our patient remains neurologically intact with resolution of his chest and back pain. Conclusions Because of its rarity, location, and radical treatment approach, we considered this case worthy of reporting. The solid variant of aneurysmal bone cyst is difficult to diagnose radiologically before biopsy or surgery, and we hope to remind other physicians that it should be included in the differential diagnosis of any lytic expansile destructive lesion of the spine. PMID:21718507

Palaeobiological implications of the bone histology of Pterodaustro guinazui.

PubMed

Chinsamy, Anusuya; Codorniú, Laura; Chiappe, Luis

2009-09-01

This study provides a comprehensive investigation of the bone microstructure of multiple bones of the Early Cretaceous filter-feeder, Pterodaustro guinazui, from the Largacito Formation of Central Argentina. We provide information regarding the bone histology of multiple elements from single skeletons, as well as a variety of bones from different individuals. In addition, we analysed changes in bone microstructure through ontogeny in growth series of several long bones of the taxon. Our investigation of skeletal and ontogenetic variation in Pterodaustro gives insights into the developmental growth dynamics of this unusual ctenochasmatid pterodactyloid from early ontogeny through to adulthood and also provides information pertaining to histological variability within and between bones of individuals. This study also documents the presence of what appears to be medullary bone tissue within the medullary cavity of a large femur of Pterodaustro. This suggests that, like birds, reproductively active female pterosaurs may have deposited a special bone tissue (medullary bone) to cope with the demand of calcium during eggshelling. Our study supports the hypothesis that small Jurassic pterodactyloids took several years to reach adult body size. More specifically, we provide data that suggests that Pterodaustro attained sexual maturity at about 2 years of age, and continued to grow for a further 3-4 years doubling in size before attaining skeletal maturity. (c) 2009 Wiley-Liss, Inc.

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

USDA-ARS?s Scientific Manuscript database

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

Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report.

PubMed

Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Watanabe, Koji; Miwa, Shinji; Tsuchiya, Hiroyuki

2015-12-07

In a previous report, we described a method of reconstruction using tumor-bearing autograft treated by liquid nitrogen for malignant bone tumor. Here we present the first case of bone deformity correction following a tumor-bearing frozen autograft via three-dimensional computerized reconstruction after multiple surgeries. A 16-year-old female student presented with pain in the left lower leg and was diagnosed with a low-grade central tibial osteosarcoma. Surgical bone reconstruction was performed using a tumor-bearing frozen autograft. Bone union was achieved at 7 months after the first surgical procedure. However, local tumor recurrence and lung metastases occurred 2 years later, at which time a second surgical procedure was performed. Five years later, the patient developed a 19° varus deformity and underwent a third surgical procedure, during which an osteotomy was performed using the Taylor Spatial Frame three-dimensional external fixation technique. A fourth corrective surgical procedure was performed in which internal fixation was achieved with a locking plate. Two years later, and 10 years after the initial diagnosis of tibial osteosarcoma, the bone deformity was completely corrected, and the patient's limb function was good. We present the first report in which a bone deformity due to a primary osteosarcoma was corrected using a tumor-bearing frozen autograft, followed by multiple corrective surgical procedures that included osteotomy, three-dimensional external fixation, and internal fixation.

Firewalls Prevent Systemic Dissemination of Vectors Derived from Human Adenovirus Type 5 and Suppress Production of Transgene-Encoded Antigen in a Murine Model of Oral Vaccination

PubMed Central

Revaud, Julien; Unterfinger, Yves; Rol, Nicolas; Suleman, Muhammad; Shaw, Julia; Galea, Sandra; Gavard, Françoise; Lacour, Sandrine A.; Coulpier, Muriel; Versillé, Nicolas; Havenga, Menzo; Klonjkowski, Bernard; Zanella, Gina; Biacchesi, Stéphane; Cordonnier, Nathalie; Corthésy, Blaise; Ben Arous, Juliette; Richardson, Jennifer P.

2018-01-01

To define the bottlenecks that restrict antigen expression after oral administration of viral-vectored vaccines, we tracked vectors derived from the human adenovirus type 5 at whole body, tissue, and cellular scales throughout the digestive tract in a murine model of oral delivery. After intragastric administration of vectors encoding firefly luciferase or a model antigen, detectable levels of transgene-encoded protein or mRNA were confined to the intestine, and restricted to delimited anatomical zones. Expression of luciferase in the form of multiple small bioluminescent foci in the distal ileum, cecum, and proximal colon suggested multiple crossing points. Many foci were unassociated with visible Peyer's patches, implying that transduced cells lay in proximity to villous rather than follicle-associated epithelium, as supported by detection of transgene-encoded antigen in villous epithelial cells. Transgene-encoded mRNA but not protein was readily detected in Peyer's patches, suggesting that post-transcriptional regulation of viral gene expression might limit expression of transgene-encoded antigen in this tissue. To characterize the pathways by which the vector crossed the intestinal epithelium and encountered sentinel cells, a fluorescent-labeled vector was administered to mice by the intragastric route or inoculated into ligated intestinal loops comprising a Peyer's patch. The vector adhered selectively to microfold cells in the follicle-associated epithelium, and, after translocation to the subepithelial dome region, was captured by phagocytes that expressed CD11c and lysozyme. In conclusion, although a large number of crossing events took place throughout the intestine within and without Peyer's patches, multiple firewalls prevented systemic dissemination of vector and suppressed production of transgene-encoded protein in Peyer's patches. PMID:29423380

CAN ULTRASOUND ABDOMEN HELP IN EARLY DIAGNOSIS OF DIABETES MELLITUS? AN OBSERVATIONAL STUDY.

PubMed

Anwar, Javed; Aamir, Muhammad Omer; Sanaullah; Imdad, Zeeshan ul Hasnain; Parveen, Ishrat; Yousaf, Nasreen

2015-01-01

Diabetes mellitus is a common disease. Similarly, ultrasound findings of fatty change and renal crystals are commonly seen on ultrasound. In the personal observation of the main author over the past so many years it was noticed that Diabetes Mellitus, Fatty liver and renal crystals all sit well together. This study tries to establish a relationship between diabetes mellitus renal echogenic foci and fatty liver. This study is first of its kind, as nobody has ever before investigated an association between the renal echogenic foci and fatty liver in relation to diabetes mellitus. This cross-sectional, observational study was conducted at Radiology Department Combined Military Hospital, Kohat From 2nd June 2013 to 30th May 2014. Three hundred patients were collected on the basis of having fatty liver and renal echogenic foci on ultrasound and three hundred more patients were collected who had no fatty liver or renal echogenic foci on ultrasound. Their labs were done for diabetes mellitus. The patients having renal echogenic foci together with fatty liver had 83% positive rate of being diabetics, while patients with no fatty liver and no echogenic foci on ultrasonography had only 0.6% Positive rate of being diabetics. Our results provided the first demonstration of an association between renal echogenic foci together with fatty liver with the diabetes mellitus. Thus ultrasound examination of abdomen can be helpful in its early diagnosis if we make a protocol of doing fasting and random blood sugars in all those patients who have positive renal echogenic foci and fatty liver on their ultrasound examination.

Multiple Small Diameter Drillings Increase Femoral Neck Stability Compared with Single Large Diameter Femoral Head Core Decompression Technique for Avascular Necrosis of the Femoral Head.

PubMed

Brown, Philip J; Mannava, Sandeep; Seyler, Thorsten M; Plate, Johannes F; Van Sikes, Charles; Stitzel, Joel D; Lang, Jason E

2016-10-26

Femoral head core decompression is an efficacious joint-preserving procedure for treatment of early stage avascular necrosis. However, postoperative fractures have been described which may be related to the decompression technique used. Femoral head decompressions were performed on 12 matched human cadaveric femora comparing large 8mm single bore versus multiple 3mm small drilling techniques. Ultimate failure strength of the femora was tested using a servo-hydraulic material testing system. Ultimate load to failure was compared between the different decompression techniques using two paired ANCOVA linear regression models. Prior to biomechanical testing and after the intervention, volumetric bone mineral density was determined using quantitative computed tomography to account for variation between cadaveric samples and to assess the amount of bone disruption by the core decompression. Core decompression, using the small diameter bore and multiple drilling technique, withstood significantly greater load prior to failure compared with the single large bore technique after adjustment for bone mineral density (p< 0.05). The 8mm single bore technique removed a significantly larger volume of bone compared to the 3mm multiple drilling technique (p< 0.001). However, total fracture energy was similar between the two core decompression techniques. When considering core decompression for the treatment of early stage avascular necrosis, the multiple small bore technique removed less bone volume, thereby potentially leading to higher load to failure.

Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis.

PubMed

Flore, R; Ponziani, F R; Di Rienzo, T A; Zocco, M A; Flex, A; Gerardino, L; Lupascu, A; Santoro, L; Santoliquido, A; Di Stasio, E; Chierici, E; Lanti, A; Tondi, P; Gasbarrini, A

2013-09-01

Vascular calcification and osteoporosis share similar etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so called "calcium paradox", that is the lack of calcium in the bone and its storage in the vessel wall. These events may have clinically relevant consequences, such as cardiovascular accidents, and bone fractures. To review the biological function of vitamin K2 metabolism, the main factors related to its deficiency and the consequent clinical significance. Vitamin K2 is essential for the function of several proteins, involved in the maintenance of the normal structure of arterial wall, osteoarticular system, teeth, and for the regulation of cell growth. It has been demonstrated to have a pivotal role in the inhibition of vascular foci of calcification, and in the regulation of calcium deposition in the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy population. This deficiency is related to the interaction of various factors, such as the reduced dietary intake, the alteration of intestinal absorption or production, with a possible role of intestinal microbiota and the increased consumption at the vessel wall. Vitamin K2 deficiency has recently been recognized as a protagonist in the development of vascular calcification and osteoporosis. Data reported so far are promising and, dietary supplementation seems a useful tool to contrast these diseases. However, large studies or solid clinical correlations regarding vitamin K2 deficiency and its pathologic consequences are needed to confirm these preliminary experiences.

Automated analysis of time-lapse fluorescence microscopy images: from live cell images to intracellular foci.

PubMed

Dzyubachyk, Oleh; Essers, Jeroen; van Cappellen, Wiggert A; Baldeyron, Céline; Inagaki, Akiko; Niessen, Wiro J; Meijering, Erik

2010-10-01

Complete, accurate and reproducible analysis of intracellular foci from fluorescence microscopy image sequences of live cells requires full automation of all processing steps involved: cell segmentation and tracking followed by foci segmentation and pattern analysis. Integrated systems for this purpose are lacking. Extending our previous work in cell segmentation and tracking, we developed a new system for performing fully automated analysis of fluorescent foci in single cells. The system was validated by applying it to two common tasks: intracellular foci counting (in DNA damage repair experiments) and cell-phase identification based on foci pattern analysis (in DNA replication experiments). Experimental results show that the system performs comparably to expert human observers. Thus, it may replace tedious manual analyses for the considered tasks, and enables high-content screening. The described system was implemented in MATLAB (The MathWorks, Inc., USA) and compiled to run within the MATLAB environment. The routines together with four sample datasets are available at http://celmia.bigr.nl/. The software is planned for public release, free of charge for non-commercial use, after publication of this article.

Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications

NASA Technical Reports Server (NTRS)

Charles, H. K. Jr; Beck, T. J.; Feldmesser, H. S.; Magee, T. C.; Spisz, T. S.; Pisacane, V. L.

2001-01-01

An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

PubMed

Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

2018-05-01

Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX

PubMed Central

McDonald, Robert J.; Ekins, Jacob B.; Tin, Anthony S.; Costes, Sylvain; Hudson, Tamara M.; Schroeder, Dana J.; Kallmes, Kevin; Kaufmann, Scott H.; Young, Philip M.; Lu, Aiming; Kadirvel, Ramanathan; Kallmes, David F.

2018-01-01

Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR) exam. Sixty patients were enrolled (median age 55 years, 39 males). Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90), but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140). Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25%) increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure. PMID:29309426

X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

PubMed

Schwab, Siegfried A; Brand, Michael; Schlude, Ina-Kristin; Wuest, Wolfgang; Meier-Meitinger, Martina; Distel, Luitpold; Schulz-Wendtland, Ruediger; Uder, Michael; Kuefner, Michael A

2013-01-01

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. 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. 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. 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.

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

PubMed

Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

Persistence of γ-H2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to γ-rays or iron ions.

PubMed

Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V; Helen Barcellos-Hoff, Mary; Parvin, Bahram; Rydberg, Bjorn

2011-07-01

To investigate γ-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionising radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced γ-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both γ-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after γ-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. The disappearance of radiation-induced γ-H2AX and 53BP1 foci in HMEC has different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent γ-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double-strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodelling.

THE LIVER OF WOODCHUCKS CHRONICALLY INFECTED WITH THE WOODCHUCK HEPATITIS VIRUS CONTAINS FOCI OF VIRUS CORE ANTIGEN NEGATIVE HEPATOCYTES WITH BOTH ALTERED AND NORMAL MORPHOLOGY

PubMed Central

Xu, Chunxiao; Yamamoto, Toshiki; Zhou, Tianlun; Aldrich, Carol E.; Frank, Katy; Cullen, John M.; Jilbert, Allison R.; Mason, William S.

2007-01-01

The livers of woodchucks chronically infected with woodchuck hepatitis virus (WHV) contain foci of morphologically altered hepatocytes (FAH) with “basophilic”, “amphophilic” and “clear cell” phenotypes, which are possibly pre-neoplastic in nature. Interestingly, most fail to express detectable levels of WHV proteins and nucleic acids. We studied sections of WHV-infected liver tissue to determine if all foci of hepatocytes that failed to express detectable levels of WHV, as assessed by immunoperoxidase staining for WHV core antigen, could be classified morphologically as FAH. We found that at least half of the foci of WHV core antigen negative hepatocytes did not show clear morphological differences in either H&E or PAS (periodic acid Schiff) stained sections from surrounding hepatocytes, and were therefore not designated as FAH. In the second approach, we assayed core antigen negative foci for the presence of fetuin B, a serum protein produced by normal hepatocytes, but not by neoplastic hepatocytes in hepatocellular carcinomas. Basophilic and amphophilic FAH had reduced levels of fetuin B compared to hepatocytes present in the surrounding liver; fetuin B staining was detected in clear cell FAH but the level could not be accurately assessed because of the displacement of fetuin B to the cell periphery by accumulated glycogen. The foci of morphologically normal WHV core antigen negative hepatocytes had similar levels of fetuin B to that of the surrounding hepatocytes. The co-existence of at least four types of WHV core antigen negative foci, including those with no obvious morphologic changes, raises the possibility that the different foci arise from distinct primary events. We hypothesize that a common event is loss of the ability to express WHV, allowing these hepatocytes to escape immune mediated cell death and to undergo clonal expansion to form distinct foci. PMID:17078989

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

PubMed Central

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

2011-01-01

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. PMID:21149353

Chromatin insulator bodies are nuclear structures that form in response to osmotic stress and cell death

PubMed Central

Schoborg, Todd; Rickels, Ryan; Barrios, Josh

2013-01-01

Chromatin insulators assist in the formation of higher-order chromatin structures by mediating long-range contacts between distant genomic sites. It has been suggested that insulators accomplish this task by forming dense nuclear foci termed insulator bodies that result from the coalescence of multiple protein-bound insulators. However, these structures remain poorly understood, particularly the mechanisms triggering body formation and their role in nuclear function. In this paper, we show that insulator proteins undergo a dramatic and dynamic spatial reorganization into insulator bodies during osmostress and cell death in a high osmolarity glycerol–p38 mitogen-activated protein kinase–independent manner, leading to a large reduction in DNA-bound insulator proteins that rapidly repopulate chromatin as the bodies disassemble upon return to isotonicity. These bodies occupy distinct nuclear territories and contain a defined structural arrangement of insulator proteins. Our findings suggest insulator bodies are novel nuclear stress foci that can be used as a proxy to monitor the chromatin-bound state of insulator proteins and provide new insights into the effects of osmostress on nuclear and genome organization. PMID:23878275

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice.

PubMed

Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Kodama, Yukio; Yoshida, Midori

2016-01-01

To clarify the major pathway of liver tumor development induced by imazalil (IMA), an imidazole fungicide, male constitutive androstane receptor (CAR)-knockout (CARKO) and wild-type (WT) mice were treated with IMA at 500 ppm in the diet up to 27 weeks after initiation by diethylnitrosamine. After 27 weeks of treatment, neither altered foci nor adenomas were significantly increased in CARKO mice, whereas both eosinophilic altered foci and adenomas were increased in WT mice. After 4 or 13 weeks of IMA treatment, liver hypertrophy was observed at the tumor-inducible dose without differences among genotypes or durations. Analysis of hepatic drug metabolite enzymes, performed after administration of multiple doses during a 1-week period, indicated that pregnane X receptor might be involved in liver hypertrophy because IMA markedly elevated Cyp3a11 and Cyp2b10 expression levels in a dose-dependent manner in both genotypes. Our results demonstrated that the CAR pathway was the main mechanism of liver tumor development induced by IMA. The carcinogenic pathway was different from that of liver hypertrophy.

Synchronous occurrence of prostate carcinoma and multiple myeloma: a case report.

PubMed

Sehgal, Tushar; Sharma, Sudha; Naseem, Shano; Varma, Neelam; Das, Ashim; Sharma, S C

2014-09-01

We describe a rare case of metastatic prostate cancer to bone marrow and synchronous multiple myeloma as the second malignant disease. Various diagnostic procedures, including cytomorphology and immunohistochemistry analyses together contributed to the detection of metastasis of prostate cancer and synchronous plasma cell proliferation in the bone marrow. The association between these two disorders is poorly understood however, some studies show that bone marrow microenvironment may play a crucial role. The need for further research in this regard is required to unfold this fascinating association.

The first taste is always with the eyes: a meta-analysis on the neural correlates of processing visual food cues.

PubMed

van der Laan, L N; de Ridder, D T D; Viergever, M A; Smeets, P A M

2011-03-01

Food selection is primarily guided by the visual system. Multiple functional neuro-imaging studies have examined the brain responses to visual food stimuli. However, the results of these studies are heterogeneous and there still is uncertainty about the core brain regions involved in the neural processing of viewing food pictures. The aims of the present study were to determine the concurrence in the brain regions activated in response to viewing pictures of food and to assess the modulating effects of hunger state and the food's energy content. We performed three Activation Likelihood Estimation (ALE) meta-analyses on data from healthy normal weight subjects in which we examined: 1) the contrast between viewing food and nonfood pictures (17 studies, 189 foci), 2) the modulation by hunger state (five studies, 48 foci) and 3) the modulation by energy content (seven studies, 86 foci). The most concurrent brain regions activated in response to viewing food pictures, both in terms of ALE values and the number of contributing experiments, were the bilateral posterior fusiform gyrus, the left lateral orbitofrontal cortex (OFC) and the left middle insula. Hunger modulated the response to food pictures in the right amygdala and left lateral OFC, and energy content modulated the response in the hypothalamus/ventral striatum. Overall, the concurrence between studies was moderate: at best 41% of the experiments contributed to the clusters for the contrast between food and nonfood. Therefore, future research should further elucidate the separate effects of methodological and physiological factors on between-study variations. Copyright © 2010 Elsevier Inc. All rights reserved.

The formation of inflammatory demyelinated lesions in cerebral white matter

PubMed Central

Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

2016-01-01

Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

[A case of chronic multifocal myositis].

PubMed

Maruyama, T; Kondo, K; Tabata, K; Yanagisawa, N

1992-11-01

A 61-year-old civil engineer began to have slowly progressive muscle atrophy in the right shoulder and the left arm at 56 years of age. Muscle wasting became manifest in the left thigh at 59 years and in the right thigh at 60 years. He had mild difficulty in climbing and descending stairs. On examination, although he had notable muscle atrophy in the right trapezius and proximal muscles in the upper and lower extremities, his muscle strength was relatively well preserved. The muscle atrophy was asymmetrical; the right periscapular region and the left upper and lower extremities were more markedly atrophic. In addition, multiple foci of the striking muscle atrophy were noted in the upper trunk and the proximal limb muscles. Fasciculation was not present. Deep tendon reflexes were normal with no pathologic reflexes. Except for a moderately elevated serum creatine kinase level of 709 Ul/l (normal 40-170) and mildly elevated serum myoglobin level of 100 ng/ml (normal < 60), no laboratory tests showed abnormal values suggesting an inflammatory process. Motor and sensory nerve conduction velocities were within normal limits. Electromyography disclosed myopathic and neuropathic changes. Computed tomography (CT) of skeletal muscles showed asymmetrical muscle atrophy and patchy low-density foci. In biopsied left quadriceps and right gastrocnemius muscles which showed partially low density on CT, there was marked variation in muscle fiber size, with necrotic and regenerating fibers, an increased number of centrally placed nuclei, and interstitial fibrosis. There were numerous foci of mononuclear inflammatory cellular infiltration, especially around the blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

The formation of inflammatory demyelinated lesions in cerebral white matter.

PubMed

Maggi, Pietro; Macri, Sheila M Cummings; Gaitán, María I; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L; Ellis, Mary; Wu, Tianxia; Silva, Afonso C; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S

2014-10-01

Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. On average, BBB permeability increased 3.5-fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001). This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. © 2014 American Neurological Association.

Bone Marrow Diseases - Multiple Languages

MedlinePlus

... Marrow Biopsy - العربية (Arabic) Bilingual PDF Health Information Translations Chinese, Simplified (Mandarin dialect) (简体中文) Expand Section Bone ... Chinese, Simplified (Mandarin dialect)) Bilingual PDF Health Information Translations Chinese, Traditional (Cantonese dialect) (繁體中文) Expand Section Bone ...

[Secondary osteoporosis or secondary contributors to bone loss in fracture. Endocrinological aspects of bone metabolism].

PubMed

Fukumoto, Seiji

2013-09-01

Bone works to play essential roles in mineral metabolism and hematopoiesis as well as to support our body and protect internal organs as a hard tissue. In order to accomplish these multiple functions, bone needs to communicate with other organs. Endocrine system functions as one of the communication pathways between bone and other organs. It has been known that bone is a target organ of many hormones. In addition, it has been established that bone itself produces hormones and works as an endocrine organ.

Origins of recently emerged foci of the tick Dermacentor reticulatus in central Europe inferred from molecular markers.

PubMed

Kloch, Agnieszka; Mierzejewska, Ewa J; Karbowiak, Grzegorz; Slivinska, Kateryna; Alsarraf, Mohammed; Rodo, Anna; Kowalec, Maciej; Dwużnik, Dorota; Didyk, Yuliya M; Bajer, Anna

2017-04-15

The ornate dog tick Dermacentor reticulatus is vector of several blood parasites, including Babesia canis, a causative agent of babesiosis. The geographical range of D. reticulatus in Europe is discontinuous with a gap separating eastern and western macroregions. New foci observed in several locations in western and central Europe were considered an expansion of the western population, including foci in western Poland. In the present paper we used molecular markers to identify the origins of these foci, and we compared their genetic polymorphism to D. reticulatus collected in sites situated within the eastern population. The overall polymorphism in mt 16S rDNA was low, and all sites from the western population shared the same haplotype suggesting the expansion in this area. In the marker 5.8S rDNA-ITS2 we found no differences in polymorphism between sites from eastern Poland (eastern population), and newly emerged foci in western Poland considered a putative expansion zone of the western population. However, the sites from western Poland differed considerably from nearby German site. Our results show that foci in western Poland could not have originated from D. reticulatus from the western population, as previously thought. We found that the state border following river hinders considerably gene flow between adjacent sites what suggest that natural dispersal of D. reticulatus by wildlife is unlikely, and the emergence of new foci should rather be contributed to human-associated dispersal. We propose that livestock, and pets travelling with their owners are the most probable source of new foci, and they can easily transfer ticks within a country but not between countries. Copyright © 2017 Elsevier B.V. All rights reserved.

Automatic detection of DNA double strand breaks after irradiation using an γH2AX assay.

PubMed

Hohmann, Tim; Kessler, Jacqueline; Grabiec, Urszula; Bache, Matthias; Vordermark, Dyrk; Dehghani, Faramarz

2018-05-01

Radiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations. Therefore, we present a method to automatically analyze the number of foci inside nuclei, facilitating and quickening the analysis of DSBs with high reliability in fluorescent images. First nuclei were detected in fluorescent images. Afterwards, the nuclei were analyzed independently from each other with a local thresholding algorithm. This approach allowed accounting for different levels of noise and detection of the foci inside the respective nucleus, using Hough transformation searching for circles. The presented algorithm was able to correctly classify most foci in cases of "high" and "average" image quality (sensitivity>0.8) with a low rate of false positive detections (positive predictive value (PPV)>0.98). In cases of "low" image quality the approach had a decreased sensitivity (0.7-0.9), depending on the manual control counter. The PPV remained high (PPV>0.91). Compared to other automatic approaches the presented algorithm had a higher sensitivity and PPV. The used automatic foci detection algorithm was capable of detecting foci with high sensitivity and PPV. Thus it can be used for automatic analysis of images of varying quality.

Compared With Elastin Stains, h-Caldesmon and Desmin Offer Superior Detection of Vessel Invasion in Gastric, Pancreatic, and Colorectal Adenocarcinomas.

PubMed

Ekinci, Özgür; Öğüt, Betül; Çelik, Bülent; Dursun, Ayşe

2018-06-01

The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used. There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001). We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

Bone matrix, cellularity, and structural changes in a rat model with high-turnover osteoporosis induced by combined ovariectomy and a multiple-deficient diet.

PubMed

Govindarajan, Parameswari; Böcker, Wolfgang; El Khassawna, Thaqif; Kampschulte, Marian; Schlewitz, Gudrun; Huerter, Britta; Sommer, Ursula; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Szalay, Gabor; Wenisch, Sabine; Lips, Katrin S; Schnettler, Reinhard; Langheinrich, Alexander; Heiss, Christian

2014-03-01

In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellularity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved long-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineralized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The Efficacy of Cyclic Injection of Bone Morphogenetic Protein-2 in Large-Scale Calvarial Bone Defects.

PubMed

Choi, Jin Mi; Jeong, Woo Shik; Park, Eun Jung; Choi, Jong Woo

2017-03-01

Bone morphogenetic protein-2 (BMP-2) appears to be one of the most potent growth factors thus far studied. However, recent publications on the clinical application of BMP-2 revealed that its correct control is the paramount issue in clinical practice. For improving BMP-2 delivery, the cyclic administration might be an alternative. Accordingly, the authors cyclically injected BMP-2 in a cyclic injection model of large cranial defects to maintain the proper dosage during the bone healing process. A 10-mm diameter calvarial bone defect was produced using a round drill in 8-week-old Sprague-Dawley rats. Silk-hydroxyapatite scaffolds soaked in the appropriate concentration of BMP-2 were implanted into the defect. The animals were split into 4 single-injection groups and 3 multiple-injection groups; the latter groups received weekly subcutaneous injections of BMP-2 solution (1, 5, and 10 μg/mL) for 4 weeks, whereas the former groups received a single injection of BMP-2 at these concentrations. Each rat underwent computed tomography at 8 weeks. In terms of total volumes of the new bone, the 5 μg/mL multiple-injection BMP-2 group had significantly greater increases in bone volume than the single-injection groups. In terms of bone thickness, the multiple-injection groups had better outcomes than the single-injection groups. Thus, the cyclic injection protocol restored the original thickness without overgrowth. Cyclic injection of BMP-2 permits more accurate dosage control than single injection and improves thickness and dense bone regeneration. Therefore, it may represent a promising approach for future clinical trials. Further investigation using a greater number of animals is required.

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

PubMed Central

de Bakker, Chantal M. J.; Altman-Singles, Allison R.; Li, Yihan; Tseng, Wei-Ju; Li, Connie; Liu, X. Sherry

2017-01-01

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. PMID:28109138

DISSEMINATED PROTOTHECOSIS IN A RUWENZORI LONG-HAIRED FRUIT BAT ( ROUSETTUS LANOSUS).

PubMed

Stockinger, Brian G; Doster, Alan R

2017-12-01

An adult male Ruwenzori long-haired fruit bat ( Rousettus lanosus) presented for lethargy and unthriftiness. Physical examination revealed cranial alopecia, mandibular ulceration, and dehydration. Supportive care and antibiotic therapy were initiated. The bat was found dead 3 days after presentation. Necropsy revealed alopecia on the head and body, exposed dried bone on the rostral tip of the mandible, and excessive clear pleural fluid. Lungs were congested and contained miliary white foci disseminated randomly throughout the parenchyma. Subcutaneous, intra-thoracic, and intra-abdominal adipose depots were minimal. Histologic examination of skin and lung revealed the presence of algal-like organisms morphologically consistent with Prototheca spp. Polymerase chain reaction amplification revealed >99% sequence identity match with Prototheca zopfii. Protothecosis has been previously reported in a single bat, Lyle's flying fox ( Pteropus lylei), in Switzerland, but definitive protothecal speciation was not possible.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review

PubMed Central

DÍAZ-DELGADO, Josué; POOL, Roy; HOPPES, Sharman; CEREZO, Argine; QUESADA-CANALES, Óscar; STOICA, George

2017-01-01

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies. PMID:28331115

Influence of the environment and phototoxicity of the live cell imaging system at IMP microbeam facility

NASA Astrophysics Data System (ADS)

Liu, Wenjing; Du, Guanghua; Guo, Jinlong; Wu, Ruqun; Wei, Junzhe; Chen, Hao; Li, Yaning; Zhao, Jing; Li, Xiaoyue

2017-08-01

To investigate the spatiotemporal dynamics of DNA damage and repair after the ion irradiation, an online live cell imaging system has been established based on the microbeam facility at Institute of Modern Physics (IMP). The system could provide a sterile and physiological environment by making use of heating plate and live cell imaging solution. The phototoxicity was investigated through the evaluation of DNA repair protein XRCC1 foci formed in HT1080-RFP cells during the imaging exposure. The intensity of the foci induced by phototoxicity was much lower compared with that of the foci induced by heavy ion hits. The results showed that although spontaneous foci were formed due to RFP exposure during live cell imaging, they had little impact on the analysis of the recruitment kinetics of XRCC1 in the foci induced by the ion irradiation.

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

PubMed Central

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

High-dose bone morphogenetic protein-induced ectopic abdomen bone growth.

PubMed

Deutsch, Harel

2010-02-01

Infuse [bone morphogenetic protein (BMP)] is increasingly used in spinal fusion surgery. The authors report a rare complication of BMP use. This is a case report. A 55-year-old male underwent a thoracic T8 to the pelvis fusion for degenerative lumbar disc disease and pseudarthrosis at another institution. The procedure involved an anterior and posterior approach with the use of multiple units of BMP. The patient presented to our institution with complaints of weight loss, pain, tenderness, and increasing solid growth in the left lower quadrant several months after his surgery. A computed tomography revealed ectopic bone growth in the retroperitoneal area and pelvis contiguous to the anterior lumbar exposure. The anterior wound was re-explored, and a large sheet of ectopic bone was removed from the retroperitoneal space. We report a rare case of extraspinal ectopic bone growth because of the use of multiple packages of BMP. Copyright (c) 2010 Elsevier Inc. All rights reserved.

[Pregnancy and lactation are not risk factors for osteoporosis or fractures].

PubMed

Karlsson, Magnus K; Ahlborg, Henrik G; Karlsson, Caroline

Observational and case control studies infer that a pregnancy and a period of lactation are followed by loss in bone mass of up to 5%. The reason for this loss is virtually impossible to conclude as so many factors known to influence the bone mass undergo changes during a pregnancy and lactation. The increased calcium demand, changed nutritional habits, reduced smoking and alcohol consumption seen in many women during these periods, the changes in body weight and fat content, the changed level of physical activity and the changed levels of hormones with potential to influence the bone metabolism could all influence the bone mass. Most studies also report that the deficit in "bone mass" normalises after weaning. Multiple pregnancies and long total duration of lactation can not be regarded as risk factors for osteoporosis and fragility fractures as most reports indicate that women with multiple pregnancies have similar or higher bone mass and similar or lower fracture incidence than their peers with no children.

Disseminated Hemangiosarcoma in a Juvenile Rhesus Macaque (Macaca mulatta)

PubMed Central

Beck, Amanda P; Gray, Stanton B; Chaffee, Beth K

2016-01-01

Hemangiosarcoma is a malignant tumor of vascular endothelial origin that is sporadically reported in rhesus macaques. This report describes the clinicopathologic features of a 1-y-old rhesus macaque with spontaneous disseminated hemangiosarcoma that originally presented as a focal cutaneous mass. Histopathologic examination of multiple tumor foci revealed regions in which the neoplastic cells formed diffuse sheets, as well as the well-defined vascular channels typically associated with hemangiosarcoma. Multiple endothelial cell immunomarkers were used to confirm the diagnosis in this rhesus macaque. The tumor exhibited staining properties consistent with those seen in domestic animals and humans. In addition, to our knowledge, this animal represents the youngest case of any form of spontaneous hemangiosarcoma reported in the rhesus macaque to date. PMID:27298251

Disseminated Hemangiosarcoma in a Juvenile Rhesus Macaque (Macaca mulatta).

PubMed

Beck, Amanda P; Gray, Stanton B; Chaffee, Beth K

2016-01-01

Hemangiosarcoma is a malignant tumor of vascular endothelial origin that is sporadically reported in rhesus macaques. This report describes the clinicopathologic features of a 1-y-old rhesus macaque with spontaneous disseminated hemangiosarcoma that originally presented as a focal cutaneous mass. Histopathologic examination of multiple tumor foci revealed regions in which the neoplastic cells formed diffuse sheets, as well as the well-defined vascular channels typically associated with hemangiosarcoma. Multiple endothelial cell immunomarkers were used to confirm the diagnosis in this rhesus macaque. The tumor exhibited staining properties consistent with those seen in domestic animals and humans. In addition, to our knowledge, this animal represents the youngest case of any form of spontaneous hemangiosarcoma reported in the rhesus macaque to date.

A Tikhonov Regularization Scheme for Focus Rotations with Focused Ultrasound Phased Arrays

PubMed Central

Hughes, Alec; Hynynen, Kullervo

2016-01-01

Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually-driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations. PMID:27913323

A Tikhonov Regularization Scheme for Focus Rotations With Focused Ultrasound-Phased Arrays.

PubMed

Hughes, Alec; Hynynen, Kullervo

2016-12-01

Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound-phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations.

Efficient multi-site two-photon functional imaging of neuronal circuits.

PubMed

Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R

2016-12-01

Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms.

Efficient multi-site two-photon functional imaging of neuronal circuits

PubMed Central

Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R.

2016-01-01

Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms. PMID:28018745

Total bone calcium in normal women: effect of age and menopause status

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

Gallagher, J.C.; Goldgar, D.; Moy, A.

1987-12-01

Bone density in different regions of the skeleton was measured in 392 normal women aged 20-80 years by dual photon absorpiometry. In premenopausal women, aged 25-50 years, multiple regression analysis of regional bone density on age, height, and weight showed a small significant decrease in total bone density (less than 0.01) but no significant change in other regions of the skeleton. In postmenopausal women there were highly significant decreases in all regions of the skeleton (p less than 0.001), and bone density in these areas decreased as a logarithmic function of years since menopause. Based on multiple regression analyses, themore » decrease in spine density and total bone calcium was 2.5-3.0 times greater in the 25 years after menopause than the 25 years before menopause. The largest change, however, occurred in the first five years after menopause. During this time the estimated annual change in spine density and total bone calcium was about 10 times greater than that in the premenopausal period. These results demonstrate the important effect of the menopause in determining bone mass in later life.« less

Patient-specific 3D microfluidic tissue model for multiple myeloma.

PubMed

Zhang, Wenting; Lee, Woo Y; Siegel, David S; Tolias, Peter; Zilberberg, Jenny

2014-08-01

In vitro culturing of primary multiple myeloma cells (MMC) has been a major challenge as this plasma cell malignancy depends on the bone marrow environment for its survival. Using a microfluidic platform to emulate the dynamic physiology of the bone marrow microenvironment, we report here a new approach for culturing difficult to preserve primary human MMC. The system uses a three-dimensional ossified tissue to mimic the tumor niche and recapitulate interactions between bone marrow cells and osteoblasts (OSB). To this end, the human fetal OSB cell line hFOB 1.19 was cultured in an eight-chamber microfluidic culture device to facilitate the seeding of mononuclear cells from bone marrow aspirates from three multiple myeloma patients. Optical microscopy, used for real-time monitoring of mononuclear cell interactions with the ossified tissue, confirmed that these are drawn toward the OSB layer. After 3 weeks, cocultures were characterized by flow cytometry to evaluate the amount of expansion of primary MMC (with CD138(+) and CD38(+)CD56(+) phenotypes) in this system. For each of the three patients analyzed, bone marrow mononuclear cells underwent, on an average, 2 to 5 expansions; CD38(+)CD56(+) cells underwent 1 to 3 expansions and CD138(+) cells underwent 2.5 to 4.6 expansions. This approach is expected to provide a new avenue that can facilitate: (1) testing of personalized therapeutics for multiple myeloma patients; (2) evaluation of new drugs without the need for costly animal models; and (3) studying the biology of multiple myeloma, and in particular, the mechanisms responsible for drug resistance and relapse.

Osteopathia striata with cranial sclerosis: clinical, radiological, and bone histological findings in an adolescent girl.

PubMed

Ward, L M; Rauch, F; Travers, R; Roy, M; Montes, J; Chabot, G; Glorieux, F H

2004-08-15

Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra-skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French-Canadian girl with a moderate to severe form of sporadic OS-CS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis.

Multiple Myeloma, Version 2.2016

PubMed Central

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

[THE EPIZOOTIC AND EPIDEMIC ACTIVITY OF NATURAL TULAREMIA FOCI OF DIFFERENT LANDSCAPE EPIDEMIOLOGICAL TYPES IN 2009-2014].

PubMed

Meshcheryakova, I S; Mikhailova, T V; Demidova, T N; Kormilitsyna, M I

2016-01-01

to assess the present state of the natural tularemia foci of different landscape epidemiological types, by using individual focal areas as an example. Epizootological monitoring and epidemiological analysis were conducted in the areas of natural tularemia foci of tundra (Wrangel Island), meadow-field (Central Federal District of the Russian Federation), flood-swamp (Arkhangelsk Region, Khanty-Mansi Autonomous District), and steppe (Mongolii) types. Small mammals (organs, blood), tularemia patients' sera, and environniental objects were examined. Molecular genetic and immune serological diagnostic assays were used. The incidence of tularemia in the past decade was analyzed using the maps for the epidemiological examinations of tularemia cases and medical reports. The natural foci of tularemia were established to continue to actively operate. There were 2913 cases of tularemia in the Russian Federation in 2001 to 2014. The flood-swamp natural foci, in which there were summer transmissive tularemia outbreaks, the largest of high occurred in Khanti-Mansiysk in 2013 when a total of 1005 people fell ill, are a special epidemic hazard. Analysis of the tularemia outbreaks suggests that there is a need for continuous epizootological monitoring of the areas of natural tularemia foci for the timely prediction and prevention of epidemic complications. It is noted that there is an unfounded reduction in the scope of preventive measures, and immunoprevention in particular, and a weaker control of the antitularemia immune status in the population residing in the area of active natural foci of tularemia.

Multiple myeloma

MedlinePlus

Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

[Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses].

PubMed

Cammarata-Scalisi, Francisco; Cozar, Mónica; Grinberg, Daniel; Balcells, Susana; Asteggiano, Carla G; Martínez-Domenech, Gustavo; Bracho, Ana; Sánchez, Yanira; Stock, Frances; Delgado-Luengo, Wilmer; Zara-Chirinos, Carmen; Chacín, José Antonio

2015-04-01

Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18,000 to 1/50,000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses.

Method and apparatus for multiple-projection, dual-energy x-ray absorptiometry scanning

NASA Technical Reports Server (NTRS)

Feldmesser, Howard S. (Inventor); Magee, Thomas C. (Inventor); Charles, Jr., Harry K. (Inventor); Beck, Thomas J. (Inventor)

2007-01-01

Methods and apparatuses for advanced, multiple-projection, dual-energy X-ray absorptiometry scanning systems include combinations of a conical collimator; a high-resolution two-dimensional detector; a portable, power-capped, variable-exposure-time power supply; an exposure-time control element; calibration monitoring; a three-dimensional anti-scatter-grid; and a gantry-gantry base assembly that permits up to seven projection angles for overlapping beams. Such systems are capable of high precision bone structure measurements that can support three dimensional bone modeling and derivations of bone strength, risk of injury, and efficacy of countermeasures among other properties.

Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma

ClinicalTrials.gov

2018-02-27

Extramedullary Plasmacytoma; Isolated Plasmacytoma of Bone; Light Chain Deposition Disease; Primary Systemic Amyloidosis; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

[Bone structure in rheumatoid arthritis].

PubMed

Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

2013-07-01

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

From the Dance of the Foci to a Strophoid

ERIC Educational Resources Information Center

Jobbings, Andrew

2011-01-01

The intersection of a plane and a cone is a conic section and rotating the plane leads to a family of conics. What happens to the foci of these conics as the plane rotates? A classical result gives the locus of the foci as an oblique strophoid when the plane rotates about a tangent to the cone. The analogous curve when the plane intersects a…

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Bone-Immune Cell Crosstalk: Bone Diseases

PubMed Central

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma. PMID:26000310

Bone-immune cell crosstalk: bone diseases.

PubMed

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

Stability of Spinal Bone Lesions in Patients With Multiple Myeloma After Radiotherapy-A Retrospective Analysis of 130 Cases.

PubMed

Lang, Kristin; König, Laila; Bruckner, Thomas; Förster, Robert; Sprave, Tanja; Schlampp, Ingmar; Bostel, Tilman; Welte, Stefan; Nicolay, Nils H; Debus, Jürgen; Rief, Harald

2017-12-01

The objective of the present retrospective analysis was the response evaluation regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy (RT). Patients with multiple myeloma who had undergone spinal RT from March 2003 to May 2016 were analyzed before and 3 and 6 months after RT. Assessment of spinal stability and bone density was performed using the internationally recognized Taneichi scoring system and measurement of bone density using computed tomography imaging-based Hounsfield units. For statistical analysis, we used the Bowker test, McNemar test, and κ statistics to detect possible asymmetries in the distribution of the Taneichi score over time. We used the Student t test for comparison of the density values (Hounsfield units) before and after treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Additionally, overall survival was calculated using the Kaplan-Meier method. We evaluated 130 patients (69% male; 31% female) with multiple myeloma and a median age of 58 years. The median follow-up period was 41 months. Before treatment, 51% of the lesions were classified as unstable. At 3 and 6 months after RT, this rate had decreased to 41% (P = .0047) and 24% (P = .2393), respectively. The computed tomography measurements showed a significant increase in bone density at 3 and 6 months after RT. Acute RT-related grade 1 and 2 complications were detected in 34% of patients. Late side effects (grade 1-2) were detected in 23% of the patients. No severe grade 3 or 4 acute or late toxicities were identified. The median overall survival was 19.7 months for all patients and 6.6 months for patients with a Karnofsky performance score of ≤ 70%. To the best of our knowledge, ours is the first report to analyze the bone density and stability in patients with multiple myeloma after RT using a validated scoring system and computed tomography imaging. Palliative RT is an effective method resulting in a significant increase in bone density for local response and stability without severe RT-related toxicity. Furthermore, recalcification could already be detected at 3 months after treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of a staged plasma-focus apparatus. [pinch construction and current sheet dynamics investigation

NASA Technical Reports Server (NTRS)

Lee, J. H.; Mcfarland, D. R.; Harries, W. L.

1978-01-01

A new staged plasma-focus geometry combining two Mather-type plasma-focus guns was constructed, and the current-sheet dynamics were investigated. The production of simultaneous pairs of plasma foci was achieved. The intensities of X-ray and fusion-neutron emission were measured and found to agree with the scaling law for a plasma focus. Advantages of this new geometry include the possibility of using plasma-focus type pinches in multiple arrays at power levels beyond the validity regime of the current scaling law for a single gun.

Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

PubMed

Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M; Zhao, Ming

2015-10-13

Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

Biomimetics of Bone Implants: The Regenerative Road.

PubMed

Brett, Elizabeth; Flacco, John; Blackshear, Charles; Longaker, Michael T; Wan, Derrick C

2017-01-01

The current strategies for healing bone defects are numerous and varied. At the core of each bone healing therapy is a biomimetic mechanism, which works to enhance bone growth. These range from porous scaffolds, bone mineral usage, collagen, and glycosaminoglycan substitutes to transplanted cell populations. Bone defects face a range of difficulty in their healing, given the composite of dense outer compact bone and blood-rich inner trabecular bone. As such, the tissue possesses a number of inherent characteristics, which may be clinically harnessed as promoters of bone healing. These include mechanical characteristics, mineral composition, native collagen content, and cellular fraction of bone. This review charts multiple biomimetic strategies to help heal bony defects in large and small osseous injury sites, with a special focus on cell transplantation.

Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

PubMed

Mateo, Lourdes; Holgado, Susana; Mariñoso, Maria Luisa; Pérez-Andrés, Ricard; Bonjoch, Anna; Romeu, Joan; Olivé, Alejandro

2016-05-01

Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.

Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

NASA Astrophysics Data System (ADS)

Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

2016-03-01

Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

Characterization of Aes nuclear foci in colorectal cancer cells

PubMed Central

Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M. Mark

2016-01-01

Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. PMID:26229111

DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy.

PubMed

Kinashi, Yuko; Yokomizo, Natsuya; Takahashi, Sentaro

2017-04-01

To use the 53BP1 foci assay to detect DNA double-strand breaks induced by fractionated neutron beam irradiation of normal cells. The Kyoto University Research Reactor heavy-water facility and gamma-ray irradiation system were used as experimental radiation sources. After fixation of Chinese Hamster Ovary cells with 3.6% formalin, immunofluorescence staining was performed. Number and size of foci were analyzed using ImageJ software. Fractionated neutron irradiation induced 25% fewer 53BP1 foci than single irradiation at the same dose. By contrast, gamma irradiation induced 30% fewer 53BP1 foci than single irradiation at the same dose. Fractionated neutron irradiation induced larger foci than gamma irradiation, raising the possibility that persistent unrepaired DNA damage was amplified due to the high linear energy transfer component in the neutron beam. Unrepaired cluster DNA damage was more prevalent after fractionated neutron irradiation than after gamma irradiation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Pamidronate Injection

MedlinePlus

... also used along with cancer chemotherapy to treat bone damage caused by multiple myeloma (cancer that begins ... by breast cancer that has spread to the bones. Pamidronate is also used to treat Paget's disease ( ...

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice.

PubMed

Piconese, Silvia; Costanza, Massimo; Musio, Silvia; Tripodo, Claudio; Poliani, Pietro L; Gri, Giorgia; Burocchi, Alessia; Pittoni, Paola; Gorzanelli, Andrea; Colombo, Mario P; Pedotti, Rosetta

2011-04-01

Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtained in Kit(W-sh/W-sh) and in Kit(W/W-v) mice were because of the different immunization protocols, we induced EAE in these two strains with varying doses of MOG(35-55) and adjuvants. Although Kit(W-sh/W-sh) mice exhibited exacerbated EAE under all immunization protocols, Kit(W/W-v) mice were protected from EAE only when immunized with high, but not low, doses of antigen and adjuvants. Kit(W-sh/W-sh) mice reconstituted systemically, but not in the CNS, with bone marrow-derived MCs still developed exacerbated EAE, indicating that protection from disease could be exerted by MCs mainly in the CNS, and/or by other cells possibly dysregulated in Kit(W-sh/W-sh) mice. In summary, these data suggest to reconsider MC contribution to EAE, taking into account the variables of using different experimental models and immunization protocols.

Mousepox detected in a research facility: case report and failure of mouse antibody production testing to identify Ectromelia virus in contaminated mouse serum.

PubMed

Labelle, Philippe; Hahn, Nina E; Fraser, Jenelle K; Kendall, Lonnie V; Ziman, Melanie; James, Edward; Shastri, Nilabh; Griffey, Stephen M

2009-04-01

An outbreak of mousepox in a research institution was caused by Ectromelia-contaminated mouse serum that had been used for bone marrow cell culture and the cells subsequently injected into the footpads of mice. The disease initially was diagnosed by identification of gross and microscopic lesions typical for Ectromelia infection, including foci of necrosis in the liver and spleen and eosinophilic intracytoplasmic inclusion bodies in the skin. The source of infection was determined by PCR analysis to be serum obtained from a commercial vendor. To determine whether viral growth in tissue culture was required to induce viral infection, 36 mice (BALB/cJ, C57BL/6J) were experimentally exposed intraperitoneally, intradermally (footpad), or intranasally to contaminated serum or bone marrow cell cultures using the contaminated serum in the culture medium. Mice were euthanized when clinical signs developed or after 12 wk. Necropsy, PCR of spleen, and serum ELISA were performed on all mice. Mice injected with cell cultures and their cage contacts developed mousepox, antibodies to Ectromelia, and lesions, whereas mice injected with serum without cells did not. Mouse antibody production, a tool commonly used to screen biologic materials for viral contamination, failed to detect active Ectromelia contamination in mouse serum.

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response.

PubMed

Luo, Man; Bao, Zhengqiang; Xu, Feng; Wang, Xiaohui; Li, Fei; Li, Wen; Chen, Zhihua; Ying, Songmin; Shen, Huahao

2018-04-14

The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow-derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation. Genetic ablation or chemical inhibition of the DNA damage response sensor amplified the production of cytokines including Cxcl1, Cxcl2 and Ifn-γ after PM stimulation in bone marrow-derived macrophages. Similar to that seen in vitro , mice with myeloid-specific deletion of RAD50 showed higher levels of airway inflammation in response to the PM challenge, suggesting a protective role of DNA damage sensor during inflammation. These data demonstrate that PM exposure induces DNA damage and activation of DNA damage response sensor MRN complex in macrophages. Disruption of MRN complex lead to persistent, unrepaired DNA damage that causes elevated inflammatory response.

A comprehensive statistical classifier of foci in the cell transformation assay for carcinogenicity testing.

PubMed

Callegaro, Giulia; Malkoc, Kasja; Corvi, Raffaella; Urani, Chiara; Stefanini, Federico M

2017-12-01

The identification of the carcinogenic risk of chemicals is currently mainly based on animal studies. The in vitro Cell Transformation Assays (CTAs) are a promising alternative to be considered in an integrated approach. CTAs measure the induction of foci of transformed cells. CTAs model key stages of the in vivo neoplastic process and are able to detect both genotoxic and some non-genotoxic compounds, being the only in vitro method able to deal with the latter. Despite their favorable features, CTAs can be further improved, especially reducing the possible subjectivity arising from the last phase of the protocol, namely visual scoring of foci using coded morphological features. By taking advantage of digital image analysis, the aim of our work is to translate morphological features into statistical descriptors of foci images, and to use them to mimic the classification performances of the visual scorer to discriminate between transformed and non-transformed foci. Here we present a classifier based on five descriptors trained on a dataset of 1364 foci, obtained with different compounds and concentrations. Our classifier showed accuracy, sensitivity and specificity equal to 0.77 and an area under the curve (AUC) of 0.84. The presented classifier outperforms a previously published model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential Reporting Bias in Neuroimaging Studies of Sex Differences.

PubMed

David, Sean P; Naudet, Florian; Laude, Jennifer; Radua, Joaquim; Fusar-Poli, Paolo; Chu, Isabella; Stefanick, Marcia L; Ioannidis, John P A

2018-04-17

Numerous functional magnetic resonance imaging (fMRI) studies have reported sex differences. To empirically evaluate for evidence of excessive significance bias in this literature, we searched for published fMRI studies of human brain to evaluate sex differences, regardless of the topic investigated, in Medline and Scopus over 10 years. We analyzed the prevalence of conclusions in favor of sex differences and the correlation between study sample sizes and number of significant foci identified. In the absence of bias, larger studies (better powered) should identify a larger number of significant foci. Across 179 papers, median sample size was n = 32 (interquartile range 23-47.5). A median of 5 foci related to sex differences were reported (interquartile range, 2-9.5). Few articles (n = 2) had titles focused on no differences or on similarities (n = 3) between sexes. Overall, 158 papers (88%) reached "positive" conclusions in their abstract and presented some foci related to sex differences. There was no statistically significant relationship between sample size and the number of foci (-0.048% increase for every 10 participants, p = 0.63). The extremely high prevalence of "positive" results and the lack of the expected relationship between sample size and the number of discovered foci reflect probable reporting bias and excess significance bias in this literature.

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

NASA Astrophysics Data System (ADS)

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.

Nanoscopic exclusion between Rad51 and 53BP1 after ion irradiation in human HeLa cells

NASA Astrophysics Data System (ADS)

Reindl, Judith; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Siebenwirth, Christian; Drexler, Sophie E.; Dollinger, Günther; Friedl, Anna A.

2015-12-01

Many proteins involved in detection, signalling and repair of DNA double-strand breaks (DSB) accumulate in large number in the vicinity of DSB sites, forming so called foci. Emerging evidence suggests that these foci are sub-divided in structural or functional domains. We use stimulated emission depletion (STED) microscopy to investigate localization of mediator protein 53BP1 and recombination factor Rad51 after irradiation of cells with low linear energy transfer (LET) protons or high LET carbon ions. With a resolution better than 100 nm, STED microscopy and image analysis using a newly developed analyzing algorithm, the reduced product of the differences from the mean, allowed us to demonstrate that with both irradiation types Rad51 occupies spherical regions of about 200 nm diameter. These foci locate within larger 53BP1 accumulations in regions of local 53BP1 depletion, similar to what has been described for the localization of Brca1, CtIP and RPA. Furthermore, localization relative to 53BP1 and size of Rad51 foci was not different after irradiation with low and high LET radiation. As expected, 53BP1 foci induced by low LET irradiation mostly contained one Rad51 focal structure, while after high LET irradiation, most foci contained >1 Rad51 accumulation.

Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa

PubMed Central

Kuroda, Masako; Hirami, Yasuhiko; Hata, Masayuki; Mandai, Michiko; Takahashi, Masayo; Kurimoto, Yasuo

2014-01-01

Background The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. Methods A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch’s membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). Results The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001). Conclusion Hyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa. PMID:24591813

Carcinogenicity of by-products of disinfection in mouse and rat liver

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

Herren-Freund, S.L.; Pereira, M.A.

1986-11-01

By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of ..gamma..-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylene, and N-Cl piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform either hadmore » no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-days-old Swiss mice initiated with ethylnitrosourea (ENU). ENU at 5 and 20 ..mu..g/g caused a dose-dependent increase in liver tumors. In male mice, chloroform inhibited both spontaneous and ENU-induced liver tumors. When administered in the drinking water, chloroform inhibited, whereas phenobarbital promoted, hepatocarcinogenesis in mice.« less

The direct and indirect costs of long bone fractures in a working age US population.

PubMed

Bonafede, Machaon; Espindle, Derek; Bower, Anthony G

2013-01-01

Information regarding the burden of fractures is limited, especially among working age patients. The objective of this study was to evaluate the direct and indirect costs associated with long bone fractures in a working age population using real-world claims data. This was a claims-based retrospective analysis, comparing adult patients in the 6 months before and 6 months after a long bone fracture between 1/1/2001 and 12/31/2008 using the MarketScan Research Databases. Outcomes included direct medical costs and utilization, as well as work absenteeism and short term disability, which was available for a sub-set of the patients. Observed and adjusted incremental costs (i.e., the difference in costs before and after a fracture) were evaluated and reported in 2008 US$. A total of 208,094 patients with at least one fracture were included in the study. Six, mutually exclusive fracture cohorts were evaluated: tibia shaft (n = 49,839), radius (n = 97,585), hip (n = 11,585), femur (n = 6788), humerus (n = 29,884), and those with multiple long bone fractures (n = 12,413). Average unadjusted direct costs in the 6-months before a long bone fracture ranged from $3291 (radius) to $12,923 (hip). The average incremental direct cost increase in the 6-months following a fracture ranged from $5707 (radius) to $39,041 (multiple fractures). Incremental absenteeism costs ranged from $950 (radius) to $2600 (multiple fractures), while incremental short-term disability costs ranged from $2050 (radius) to $4600 (multiple fractures). The results of this study indicate that long bone fractures are costly, both in terms of direct medical costs and lost productivity. Workplace absences and short-term disability represent a significant component of the burden of long bone fractures. These results may not be generalizable to all patients with fractures in the US, and do not reflect the burden of undiagnosed or sub-clinical fractures.

Multiple polyps and colorectal cancer.

PubMed

Alecu, M; Simion, L; Straja, Nd; Brătucu, E

2014-01-01

Malignant degeneration as a possible course of evolution of colorectal polyps renders their diagnosis and therapeutic management a prophylactic act in the prevention of colorectal cancer (CRC). The study was conducted over a period of 3 years (2008-2011), during which 1,368 colonoscopies were performed in our service. The aim of the study was to identify patients presenting multiple colorectal polyps and to determine their risk factors for developing CRC, as well as to establish the appropriate therapeutic conduct. Presence of multiple polyps was recorded in over 40% of the patients identified with colorectal polyps of any kind. Dysplastic modifications observed during the histopathology exam presented a high incidence in the case of patients with multiple polyps, ranging from low-grade dysplasia to incipient CRC. Dysplastic modifications and carcinomatous foci were identified mostly among patients with multiple polyps.Only benign lesions or in situ carcinomas benefited from endoscopic treatment, poorly differentiated carcinomas or those invading the submucosa being treated by conventional surgery. Patients diagnosed with colorectal polyps require a rigorous post-therapy follow-up protocol, able to identify any eventual polyposis recurrence. Celsius.

Transcriptomic Profiling of High-Density Giardia Foci Encysting in the Murine Proximal Intestine.

PubMed

Pham, Jonathan K; Nosala, Christopher; Scott, Erica Y; Nguyen, Kristofer F; Hagen, Kari D; Starcevich, Hannah N; Dawson, Scott C

2017-01-01

Giardia is a highly prevalent, understudied protistan parasite causing significant diarrheal disease worldwide. Its life cycle consists of two stages: infectious cysts ingested from contaminated food or water sources, and motile trophozoites that colonize and attach to the gut epithelium, later encysting to form new cysts that are excreted into the environment. Current understanding of parasite physiology in the host is largely inferred from transcriptomic studies using Giardia grown axenically or in co-culture with mammalian cell lines. The dearth of information about the diversity of host-parasite interactions occurring within distinct regions of the gastrointestinal tract has been exacerbated by a lack of methods to directly and non-invasively interrogate disease progression and parasite physiology in live animal hosts. By visualizing Giardia infections in the mouse gastrointestinal tract using bioluminescent imaging (BLI) of tagged parasites, we recently showed that parasites colonize the gut in high-density foci. Encystation is initiated in these foci throughout the entire course of infection, yet how the physiology of parasites within high-density foci in the host gut differs from that of cells in laboratory culture is unclear. Here we use BLI to precisely select parasite samples from high-density foci in the proximal intestine to interrogate in vivo Giardia gene expression in the host. Relative to axenic culture, we noted significantly higher expression (>10-fold) of oxidative stress, membrane transporter, and metabolic and structural genes associated with encystation in the high-density foci. These differences in gene expression within parasite foci in the host may reflect physiological changes associated with high-density growth in localized regions of the gut. We also identified and verified six novel cyst-specific proteins, including new components of the cyst wall that were highly expressed in these foci. Our in vivo transcriptome data support an emerging view that parasites encyst early in localized regions in the gut, possibly as a consequence of nutrient limitation, and also impact local metabolism and physiology.

Transcriptomic Profiling of High-Density Giardia Foci Encysting in the Murine Proximal Intestine

PubMed Central

Pham, Jonathan K.; Nosala, Christopher; Scott, Erica Y.; Nguyen, Kristofer F.; Hagen, Kari D.; Starcevich, Hannah N.; Dawson, Scott C.

2017-01-01

Giardia is a highly prevalent, understudied protistan parasite causing significant diarrheal disease worldwide. Its life cycle consists of two stages: infectious cysts ingested from contaminated food or water sources, and motile trophozoites that colonize and attach to the gut epithelium, later encysting to form new cysts that are excreted into the environment. Current understanding of parasite physiology in the host is largely inferred from transcriptomic studies using Giardia grown axenically or in co-culture with mammalian cell lines. The dearth of information about the diversity of host-parasite interactions occurring within distinct regions of the gastrointestinal tract has been exacerbated by a lack of methods to directly and non-invasively interrogate disease progression and parasite physiology in live animal hosts. By visualizing Giardia infections in the mouse gastrointestinal tract using bioluminescent imaging (BLI) of tagged parasites, we recently showed that parasites colonize the gut in high-density foci. Encystation is initiated in these foci throughout the entire course of infection, yet how the physiology of parasites within high-density foci in the host gut differs from that of cells in laboratory culture is unclear. Here we use BLI to precisely select parasite samples from high-density foci in the proximal intestine to interrogate in vivo Giardia gene expression in the host. Relative to axenic culture, we noted significantly higher expression (>10-fold) of oxidative stress, membrane transporter, and metabolic and structural genes associated with encystation in the high-density foci. These differences in gene expression within parasite foci in the host may reflect physiological changes associated with high-density growth in localized regions of the gut. We also identified and verified six novel cyst-specific proteins, including new components of the cyst wall that were highly expressed in these foci. Our in vivo transcriptome data support an emerging view that parasites encyst early in localized regions in the gut, possibly as a consequence of nutrient limitation, and also impact local metabolism and physiology. PMID:28620589

Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

PubMed

Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

2017-12-08

Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways. Published by Elsevier B.V.

[Osteoporosis in all young daughters of a mother with multiple osteoporotic fractures. A case of familial osteoporosis].

PubMed

Parisi, M S; Díaz, A G; Oliveri, M B; Di Gregorio, S; Mautalen, C A

2001-01-01

We herein describe a family whose female members are all osteoporotic: a postmenopausal mother and her three premenopausal daughters. The mother aged 60 presented axial and peripheral fractures, and very low bone mineral density (BMD). She reported that her grandmother had suffered a hip fracture. The eldest daughter aged 30 suffered multiple vertebral fractures during pregnancy and lactation associated with very low BMD. In view of these observations, the other two daughters aged 29 and 27 years respectively were evaluated. BMD was found to be severely diminished according to densitometric values for osteoporosis established by WHO, but they had no history of bone fractures. Probably the strong genetic component in bone mass is responsible for the severely diminished BMD observed in all the women in this family, as well as the occurrence of bone fractures in two of them. To our knowledge, there are no similar reports in the literature. Our results evidence the importance of evaluating bone mass in the offspring of an individual presenting severe osteoporosis, in order to detect family members with low bone mass and at high risk of developing bone fractures.

A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

PubMed

Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

2015-08-01

Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

[Comparative analysis of the semiotics of disseminated pulmonary tuberculosis and exogenous allergic alveolitis in accordance with the data of computed tomography].

PubMed

Amansakhedov, R B; Limarova, I V; Perfiliev, A V; Abdullaev, R Yu; Sigaev, A T; Ergeshov, A E

2016-01-01

to improve the differential diagnosis of disseminated pulmonary tuberculosis (DPT) and exogenous allergic alveolitis (EAA) via comparative investigation of their computed tomography (CT) semiotics and identification of the most informative diagnostic criteria. 70 patients, including 40 patients with DPT in a phase of infiltration and 30 patients with acute EAA, were studied using a Somatom Emotion 16 multi-slice spiral CT scanner (Siemens). All the patients underwent spiral scanning from the upper chest aperture to the costodiaphragmatic recesses with a high CT algorithm at 0.8-mm slice thickness and a 1.5-mm step. Analysis of the spread of dissemination foci established that pathological changes were peribronchovascularly located in both nosological entities and characterized by a preponderance of septal and intrabronchial locations in DPT and by a centrilobular distribution in EAA. Centrilobular foci were more commonly poorly defined in EAA and mixed foci were observed in DPT. In the latter, peribronchovascular, centrilobular foci were revealed at a distance from the visceral pleura (the boundary of the deep and superficial lymphatic network, respectively) in 38% and more than half of the cases (62%) with the involvement of the visceral and parietal pleura; in EAA, the centrilobular foci were more often combined with the involvement of the visceral pleura in more than 92% of cases. The tree-in-bud sign was significantly more common in DPT. The latter was mostly characterized by apicocaudal regression of dissemination. In EAA, the foci were more frequently located asymmetrically. Monomorphic foci with destruction, as well as their polymorphism were seen in DPT; those without destruction were predominantly observed in EAA. CT ground glass and mosaic perfusion syndromes were significantly more often in EAA. In DPT, the visceral and parietal pleuras were involved in the process in 62% of cases and changes were also more common in the extrapleural fat. In addition to the peribronchovascular location of foci, the characteristic CT signs for DPT are a preponderance of intrabronchial and septal locations of foci, their apicocaudal regression, the presence of the CT tree-in-bud sign, and thickened extrapleural fat. EAA showed a prevalence of asymmetrical foci with centrilobular location with the involvement of the visceral pleura into the process, with the presence of CT ground glass and mosaic perfusion syndromes, as well as the bronchial lumen visualized in the peripheral segments of the lung.

5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

PubMed Central

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A.; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Background Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. Methods We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. Results A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Conclusions Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift. PMID:24204718

Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas.

PubMed

Abou-El-Ardat, Khalil; Seifert, Michael; Becker, Kerstin; Eisenreich, Sophie; Lehmann, Matthias; Hackmann, Karl; Rump, Andreas; Meijer, Gerrit; Carvalho, Beatriz; Temme, Achim; Schackert, Gabriele; Schröck, Evelin; Krex, Dietmar; Klink, Barbara

2017-04-01

The evolution of primary glioblastoma (GBM) is poorly understood. Multifocal GBM (ie, multiple synchronous lesions in one patient) could elucidate GBM development. We present the first comprehensive study of 12 GBM foci from 6 patients using array-CGH, spectral karyotyping, gene expression arrays, and next-generation sequencing. Multifocal GBMs genetically resemble primary GBMs. Comparing foci from the same patient proved their monoclonal origin. All tumors harbored alterations in the 3 GBM core pathways: RTK/PI3K, p53, and RB regulatory pathways with aberrations of EGFR and CDKN2A/B in all (100%) patients. This unexpected high frequency reflects a distinct genetic signature of multifocal GBMs and might account for their highly malignant and invasive phenotype. Surprisingly, the types of mutations in these genes/pathways were different in tumor foci from the same patients. For example, we found distinct mutations/aberrations in PTEN, TP53, EGFR, and CDKN2A/B, which therefore must have occurred independently and late during tumor development. We also identified chromothripsis as a late event and in tumors with wild-type TP53. Only 2 events were found to be early in all patients: single copy loss of PTEN and TERT promoter point mutations. Multifocal GBMs develop through parallel genetic evolution. The high frequency of alterations in 3 main pathways suggests that these are essential steps in GBM evolution; however, their late occurrence indicates that they are not founder events but rather subclonal drivers. This might account for the marked genetic heterogeneity seen in primary GBM and therefore has important implications for GBM therapy. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.

PubMed

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Suspected panosteitis in a camel.

PubMed

Levine, David G; Smith, Jennifer J; Richardson, Dean W; Brown, Valerie; Beech, Jill; Habecker, Perry; Adam, Emma

2007-08-01

A 6-month-old male Bactrian camel was examined because of a 3-week history of lameness of the left hind limb. Lameness was initially detected in the left hind limb but resolved and was detected in the right hind limb during treatment. Lameness increased during periods of rapid growth. Radiography revealed multiple small opacities of the medullary cavity of several long bones throughout treatment. Core bone biopsies of lesions in the tibiae revealed lamellar bone with areas of loose connective tissue, osteoblasts in the medullary cavity, and periosteal new bone formation, all which were consistent with panosteitis. Palliative treatment was attempted with epidural and transdermal administration of analgesics. Flunixin meglumine was administered PO, which coincided with an abrupt increase in serum creatinine concentration. Performance of multiple diagnostic bone biopsies led to remission of clinical signs of pain. Panosteitis should be a differential diagnosis for shifting limb lameness in young camels. Bone biopsies can be useful for diagnosis of panosteitis and possible relief of pain associated with the disease. Bactrian camels may be susceptible to the renal toxicity of flunixin meglumine, especially when dehydrated.

Prevalence of Temporal Bone Fractures in Patients with Mandibular Fractures Using Multidetector-Row CT.

PubMed

Ogura, I; Kaneda, T; Sasaki, Y; Buch, K; Sakai, O

2015-06-01

Temporal bone fracture after mandibular trauma is thought to be rare, and its prevalence has not been reported in the literature. The purpose of this study was to investigate the prevalence of temporal bone fractures in patients with mandibular fractures and the relationship between temporal bone fractures and the mandibular fracture location using multidetector-row computed tomography (MDCT). A prospective study was performed in 201 patients with mandibular fractures who underwent 64-MDCT scans. The mandibular fracture locations were classified as median, paramedian, angle, and condylar types. Statistical analysis for the relationship between prevalence of temporal bone fractures and mandibular fracture locations was performed using χ(2) test with Fisher's exact test. A P-value < 0.05 was considered statistically significant. The percentage of cases with temporal bone fracture was 3.0 % of all patients with mandibular fractures and 19.0 % of those with multiple mandibular fractures of paramedian and condylar type. There was a significant relationship between the incidence of temporal bone fracture and the paramedian- and condylar-type mandibular fracture (P = 0.001). Multiple mandibular fractures of paramedian and condylar type may be a stronger indicator for temporal bone fractures. This study suggests that patients with mandibular fracture, especially the paramedian and condylar type, should be examined for coexisting temporal bone fracture using MDCT.

Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism during Spaceflight and Recovery (Pro K)

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Zwart, S. R.; Shackelford, L.; Heer, M.

2009-01-01

Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

[Leishmania infantum MON-1 isolated from a golden jackal (Canis aureus) in Grande Kabylie (Algeria)].

PubMed

Bessad, A; Mouloua, K; Kherrachi, I; Benbetka, S; Benikhlef, R; Mezai, G; Harrat, Z

2012-02-01

In the north of Algeria, Leishmania infantum is responsible for two clinical forms of leishmaniasis: visceral and cutaneous leishmaniasis, for which dogs are the only proven reservoir host. In this study, the authors report, for the first time, the isolation of L. infantum from a golden jackal (Canis aureus) trapped in the Illoulen ou Malou region (Grande Kabylie). Two isolates were thus obtained from bone marrow and spleen and were identified by starch gel isoenzyme electrophoresis as L. infantum MON-1, the widespread zymodeme in the north of the country. Leishmania parasites have also been detected by polymerase chain reaction (PCR) in the biopsy of the spleen. The golden jackal, a prevalent wild canid in Northern Africa, could play a predominant role in the sylvatic foci of leishmaniasis and in the dissemination of the parasite in this region.

Columbid herpesvirus-1 in two Cooper's hawks (Accipiter cooperii) with fatal inclusion body disease.

PubMed

Pinkerton, Marie E; Wellehan, James F X; Johnson, April J; Childress, April L; Fitzgerald, Scott D; Kinsel, Michael J

2008-07-01

We report two separate naturally occurring cases of fatal herpesviral disease in Cooper's Hawks (Accipiter cooperii). Gross lesions included splenomegaly and hepatomegaly, with diffuse pale mottling or scattered small white foci. Histologic lesions included splenic and hepatic necrosis associated with eosinophilic intranuclear inclusion bodies characteristic of herpesvirus. In one case, necrosis and inclusions were also noted in bone marrow, thymus, bursa of Fabricius, thyroid gland, parathyroid gland, ceca, and the enteric system. Transmission electron microscopy demonstrated viral particles typical of herpesvirus within hepatocyte nuclei and budding from the nuclear membrane. Herpesviral DNA was amplified via polymerase chain reaction (PCR) of paraffin-embedded liver and spleen, and sequence data were consistent with columbid herpesvirus-1, an alphaherpesvirus of Rock Pigeons (Columba livia). PCR results provide evidence that this disease is transmitted to raptors via Rock Pigeons, most likely through ingestion of Rock Pigeons as prey.

THE EFFECTS OF A HIGH ANIMAL FAT DIET ON THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO TRIHALOMETHANES IN THE DRINKING WATER

EPA Science Inventory

The Effects of a High Animal Fat Diet on the Induction of Aberrant Crypt Foci in the Colons of Male F344/N Rats Exposed to Trihalomethanes in the Drinking Water

Abstract

Aberrant crypt foci (ACF), identified as the putative precursor lesion in the development of co...

Identification of Chinese plague foci from long-term epidemiological data

PubMed Central

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

Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion.

PubMed

Pan, Hsin Chuan; Lee, Soonchul; Ting, Kang; Shen, Jia; Wang, Chenchao; Nguyen, Alan; Berthiaume, Emily A; Zara, Janette N; Turner, A Simon; Seim, Howard B; Kwak, Jin Hee; Zhang, Xinli; Soo, Chia

2017-07-01

Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

Bone optical spectroscopy for the measurement of hemoglobin content

NASA Astrophysics Data System (ADS)

Hollmann, Joseph L.; Arambel, Paula; Piet, Judith; Shefelbine, Sandra; Markovic, Stacey; Niedre, Mark; DiMarzio, Charles A.

2014-05-01

Osteoporosis is a common side effect of spinal cord injuries. Blood perfusion in the bone provides an indication of bone health and may help to evaluate therapies addressing bone loss. Current methods for measuring blood perfusion of bone use dyes and ionizing radiation, and yield qualitative results. We present a device capable of measuring blood oxygenation in the tibia. The device illuminates the skin directly over the tibia with a white light source and measures the diffusely reflected light in the near infrared spectrum. Multiple source-detector distances are utilized so that the blood perfusion in skin and bone may be differentiated.

Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila

PubMed Central

Hur, Junho K.; Luo, Yicheng; Moon, Sungjin; Ninova, Maria; Marinov, Georgi K.; Chung, Yun D.; Aravin, Alexei A.

2016-01-01

The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis. PMID:27036967

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

Lupo, Janine M., E-mail: janine.lupo@ucsf.edu; Chuang, Cynthia F.; Chang, Susan M.

Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation.more » These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.« less

Melamine-induced urinary calculi in infants--sonographic manifestations and outcomes 1 year after exposure.

PubMed

Nie, Fang; Li, Xin-jie; Shang, Pan-feng; Wang, Ying

2013-04-01

In 2008, the melamine-tainted-milk incident started with reports of increased incidence of urolithiasis in infants in China. Affected children were screened for urolithiasis. The purpose of this study was to analyze sonographic characterization of infant melamine-induced urolithiasis. Transabdominal US examination was done in 603 infants with melamine-induced calculi. The imaging characteristics of calculi and hydronephrosis were analyzed. Follow-up US imaging was performed. Comet-tail sign was seen behind the calculus of <4 mm. Calculi of ≥ 4 mm were found in 299 inpatients with clear posterior border and with or without light shadowing. Solitary and multiple stones had similar incidence. Incidence of calculi in the inferior renal calyx was the highest (55.2%) in inpatients. Calculus size in inpatients age 2-3 years was smaller than that of children younger than 2 years old (P < 0.05). Inpatients age 2-3 years had the highest incidence rate (48.0%) of hydronephrosis. Calculi of <4 mm manifested as hyperechoic foci near the renal papillae, while calculi of ≥ 4 mm usually manifested as echogenic foci with visible inferior edge in the renal calyx. Hydronephrosis was a common imaging finding in inpatients ages 2-3 years.

Salivary gland oncocytes in African hedgehogs (Atelerix albiventris) mimicking cytomegalic inclusion disease.

PubMed

Brunnert, S R; Hensley, G T; Citino, S B; Herron, A J; Altman, N H

1991-07-01

The salivary glands from three African hedgehogs contained multiple foci of cytomegalic cells, which occasionally had a mild to moderate infiltrate of lymphocytes at the periphery. The cytomegalic cells were 35 to 40 microns in diameter with abundant acidophilic granular to hyalin cytoplasm. The nuclei were enlarged with clumped marginalized chromatin and a large, (6 to 8 microns in diameter) central, brightly eosinophilic nucleolus that had the appearance of an inclusion body by light microscopy. Histochemically most of the cytomegalic cells contained cytoplasmic metachromatic granules with Feyrter's thionine inclusion stain. Scattered cells at the periphery of the cytomegalic foci contained periodic acid-Schiff-positive cytoplasmic granules. Ultrastructurally the cytomegalic cells contained numerous tightly-packed, often bizarre, enlarged mitochondria that completely filled the cytoplasm. The nucleus consisted of a dense central core of chromatin associated with the nucleolus and the remaining chromatin was clumped and marginalized. Nuclear and cytoplasmic virions consistent with cytomegalovirus were not present. Histochemical stains of the nucleus for heavy metals were negative. The ultrastructural and histochemical findings of the cytomegalic cells were consistent with oncocytes. Previous reports in the literature of similar cells in the salivary glands of insectivores appear to have been erroneously described as cytomegalovirus infections.

Nanocomposites for bone tissue regeneration.

PubMed

Sahoo, Nanda Gopal; Pan, Yong Zheng; Li, Lin; He, Chao Bin

2013-04-01

Natural bone tissue possesses a nanocomposite structure that provides appropriate physical and biological properties. For bone tissue regeneration, it is crucial for the biomaterial to mimic living bone tissue. Since no single type of material is able to mimic the composition, structure and properties of native bone, nanocomposites are the best choice for bone tissue regeneration as they can provide the appropriate matrix environment, integrate desirable biological properties, and provide controlled, sequential delivery of multiple growth factors for the different stages of bone tissue regeneration. This article reviews the composition, structure and properties of advanced nanocomposites for bone tissue regeneration. It covers aspects of interest such as the biomimetic synthesis of bone-like nanocomposites, guided bone regeneration from inert biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone tissue regeneration. The design, fabrication, and in vitro and in vivo characterization of such nanocomposites are reviewed.

Protein kinases are associated with multiple, distinct cytoplasmic granules in quiescent yeast cells.

PubMed

Shah, Khyati H; Nostramo, Regina; Zhang, Bo; Varia, Sapna N; Klett, Bethany M; Herman, Paul K

2014-12-01

The cytoplasm of the eukaryotic cell is subdivided into distinct functional domains by the presence of a variety of membrane-bound organelles. The remaining aqueous space may be further partitioned by the regulated assembly of discrete ribonucleoprotein (RNP) complexes that contain particular proteins and messenger RNAs. These RNP granules are conserved structures whose importance is highlighted by studies linking them to human disorders like amyotrophic lateral sclerosis. However, relatively little is known about the diversity, composition, and physiological roles of these cytoplasmic structures. To begin to address these issues, we examined the cytoplasmic granules formed by a key set of signaling molecules, the protein kinases of the budding yeast Saccharomyces cerevisiae. Interestingly, a significant fraction of these proteins, almost 20%, was recruited to cytoplasmic foci specifically as cells entered into the G0-like quiescent state, stationary phase. Colocalization studies demonstrated that these foci corresponded to eight different granules, including four that had not been reported previously. All of these granules were found to rapidly disassemble upon the resumption of growth, and the presence of each was correlated with cell viability in the quiescent cultures. Finally, this work also identified new constituents of known RNP granules, including the well-characterized processing body and stress granule. The composition of these latter structures is therefore more varied than previously thought and could be an indicator of additional biological activities being associated with these complexes. Altogether, these observations indicate that quiescent yeast cells contain multiple distinct cytoplasmic granules that may make important contributions to their long-term survival. Copyright © 2014 by the Genetics Society of America.

Leptomeningeal contrast enhancement is associated with progression of cortical atrophy in MS: A retrospective, pilot, observational longitudinal study.

PubMed

Zivadinov, Robert; Ramasamy, Deepa P; Vaneckova, Manuela; Gandhi, Sirin; Chandra, Avinash; Hagemeier, Jesper; Bergsland, Niels; Polak, Paul; Benedict, Ralph Hb; Hojnacki, David; Weinstock-Guttman, Bianca

2017-09-01

Leptomeningeal contrast enhancement (LM CE) has been recently described in multiple sclerosis (MS) patients as a potential in vivo marker of cortical pathology. To investigate the association of LM CE and development of cortical atrophy in 50 MS patients (27 relapsing-remitting (RR) and 23 secondary-progressive (SP)) followed for 5 years. The presence and number of LM CE foci were assessed only at the 5-year follow-up using three-dimensional (3D) fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequence obtained 10 minutes after single dose of gadolinium injection on 3T scanner. The percentage change in whole brain, cortical and deep gray matter (GM) volumes, and lesion volume (LV) was measured between baseline and the 5-year follow-up. In total, 25 (50%) of MS patients had LM CE at the 5-year follow-up. Significantly more SPMS patients (12, 85.7%) had multiple LM CE foci, compared to those with RRMS (2, 18.2%) ( p = 0.001). MS patients with LM CE showed significantly greater percentage decrease in total GM (-3.6% vs -2%, d = 0.80, p = 0.006) and cortical (-3.4% vs -1.8%, d = 0.84, p = 0.007) volumes and greater percentage increase in ventricular cerebrospinal fluid (vCSF) volume (22.8% vs 9.9%, d = 0.90, p = 0.003) over the follow-up, compared to those without. In this retrospective, pilot, observational longitudinal study, the presence of LM CE was associated with progression of cortical atrophy over 5 years.

Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management

PubMed Central

Kristinsson, Sigurdur Y; Minter, Alex R; Korde, Neha; Tan, Esther; Landgren, Ola

2011-01-01

The manifestations of bone involvement in patients with multiple myeloma (MM) can have devastating clinical effects and increase mortality. Recent studies demonstrate that patients with the precursor conditions smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS) show evidence of bone disease and increased risk of fractures. The understanding of the pathogenesis of bone disease in MM has expanded in recent years. The traditional skeletal survey will probably be replaced by newer and more sensitive imaging techniques, which may have a prognostic impact and change our definition of MGUS and SMM. Bisphosphonates are recommended to prevent skeletal events in patients with MM, and have also been studied in SMM and MGUS. This article summarizes the current knowledge of bone disease in plasma cell disorders, and discusses the current standard and future role of novel imaging techniques, as well as the evidence and current guidelines for bisphosphonates in MM, SMM and MGUS. PMID:21745013

Novel PLS3 variants in X-linked osteoporosis: Exploring bone material properties.

PubMed

Balasubramanian, Meena; Fratzl-Zelman, Nadja; O'Sullivan, Rory; Bull, Mary; Fa Peel, Nicola; Pollitt, Rebecca C; Jones, Rebecca; Milne, Elizabeth; Smith, Kath; Roschger, Paul; Klaushofer, Klaus; Bishop, Nicholas J

2018-05-07

Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone-mass. Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients. Patient 1: 40-year old adult male diagnosed with IJO in childhood who re-presented with a hip fracture as an adult. Genetic analysis identified a pathogenic PLS3 hemizygous variant, c.1765del in exon 16. Patient 2: 15-year old boy with multiple vertebral fractures and bone biopsy findings suggestive of IJO who also has a diagnosis of autism spectrum disorder. Genetic analysis identified a maternally inherited PLS3 pathogenic c.1295T>A variant in exon 12. Analyses of the transiliac bone sample revealed severe reduction of trabecular volume and bone turnover indices and elevated bone matrix mineralisation. We propose that genetic testing for PLS3 should be undertaken in patients presenting with a current or previous history of IJO as this has implications for genetic counselling and cascade screening. The extensive evaluation of the transiliac biopsy sample of Patient 2 revealed a novel bone phenotype. This report includes a review of IJO and genetic causes of osteoporosis, and suggests that existing cases of IJO should be screened for PLS3. Through analysis of bone material properties in Patient 2, we can conclude that PLS3 does have a role in bone mineralisation. © 2018 Wiley Periodicals, Inc.

Solitary Plasmacytoma.

PubMed

Grammatico, Sara; Scalzulli, Emilia; Petrucci, Maria Teresa

2017-01-01

Solitary plasmacytoma is a rare disease characterized by a localized proliferation of neoplastic monoclonal plasma cells, without evidence of systemic disease. It can be subdivided into solitary bone plasmacytoma if the lesion originates in bone, or solitary extramedullary plasmacytoma if the lesion involves a soft tissue. The incidence of solitary bone plasmacytoma is higher than solitary extramedullary plasmacytoma. Also, the prognosis is different: even if both forms respond well to treatment, overall survival and progression-free survival of solitary bone plasmacytoma are poorer than solitary extramedullary plasmacytoma due to its higher rate of evolution in multiple myeloma. However, the recent advances in the diagnosis of multiple myeloma can better refine also the diagnosis of plasmacytoma. Flow cytometry studies and molecular analysis may reveal clonal plasma cells in the bone marrow; magnetic resonance imaging or 18 Fluorodeoxyglucose positron emission tomography could better define osteolytic bone lesions. A more explicit exclusion of possible occult systemic involvement can avoid cases of misdiagnosed multiple myeloma patients, which were previously considered solitary plasmacytoma and less treated, with an unavoidable poor prognosis. Due to the rarity of the disease, there is no uniform consensus about prognostic factors and treatment. Radiotherapy is the treatment of choice; however, some authors debate about the radiotherapy dose and the relationship with the response rate. Moreover, the role of surgery and chemotherapy is still under debate. Nevertheless, we must consider that the majority of studies include a small number of patients and analyze the efficacy of conventional chemotherapy; few cases are reported concerning the efficacy of novel agents.

γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes

PubMed Central

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

2016-01-01

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans. PMID:27922110

Breast Cancer Risk by Extent and Type of Atypical Hyperplasia: An Update from the Nurses’ Health Studies

PubMed Central

Collins, Laura C.; Aroner, Sarah; Connolly, James L.; Colditz, Graham A.; Schnitt, Stuart J.; Tamimi, Rulla M.

2015-01-01

Background Women with atypical hyperplasia (AH) on a benign breast biopsy (BBB) are at increased risk for the development of breast cancer. However, the relationship between type and extent of AH (atypical ductal hyperplasia (ADH) vs. atypical lobular hyperplasia (ALH)) and magnitude of breast cancer risk is not well-defined. Methods We conducted a nested case-control study of benign breast disease and breast cancer risk. Women with breast cancer and a prior BBB (cases=488) were matched to women with a prior BBB but free from breast cancer (controls=1907). BBB slides were reviewed and categorized as either non-proliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Results Among women with ADH, the inter-relationship between extent of atypia and breast cancer risk was not significant (OR=3.5; 95%CI 2.2-5.6 for 1-2 foci, OR= 2.7; 95%CI 1.4-5.1 for ≥3 foci; p=0.58). Similarly, while the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR=5.2; 95%CI 2.7-10.0 for 1-2 foci; OR=8.0; 95%CI 4.5-14.2 for ≥3 foci; p=0.66). Conclusion This analysis demonstrates that the extent of ADH or ALH did not significantly contribute to breast cancer risk. The lack of a significant dose-response relationship between extent and type of atypia and breast cancer risk suggests that it would be premature to use extent of atypia to influence management decisions in women with ADH or ALH. PMID:26565738

Extent of Atypical Hyperplasia Stratifies Breast Cancer Risk in Two Independent Cohorts of Women

PubMed Central

Degnim, Amy C.; Dupont, William D.; Radisky, Derek C.; Vierkant, Robert A.; Frank, Ryan D.; Frost, Marlene H.; Winham, Stacey J.; Sanders, Melinda E.; Smith, Jeffrey R.; Page, David L.; Hoskin, Tanya L.; Vachon, Celine M.; Ghosh, Karthik; Hieken, Tina J.; Denison, Lori A.; Carter, Jodi M.; Hartmann, Lynn C.; Visscher, Daniel W.

2016-01-01

Background Women with atypical hyperplasia (AH) on breast biopsy have a substantially increased risk of breast cancer (BC). Here we report BC risk with AH extent and subtype in two separate cohorts. Methods All samples containing AH were included from two cohorts of benign breast disease, Mayo Clinic and Nashville. Histology review quantified the number of foci of atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). BC risk was stratified for number of AH foci within AH subtypes. Results The study included 708 Mayo and 466 Nashville AH subjects. In the Mayo Cohort, increasing foci of AH was associated with a significant increase in risk of BC, both for ADH (RR’s of 2.61, 5.21, and 6.36 for 1, 2, and 3+ foci, p=0.006 for linear trend) and for ALH (RR’s of 2.56, 3.50, and 6.79 for 1, 2, and 3+ foci, p=0.001 for linear trend). In the Nashville Cohort, RR’s of BC for ADH were 2.70, 5.17, and 15.06 for 1, 2, and 3+ foci respectively (p<0.001 for linear trend); for ALH, RR’s also increased but not significantly (2.61, 3.48, and 4.02, p=0.148). Combining both Mayo and Nashville samples, risk increased significantly for 1, 2, and 3+ foci: RR’s of 2.65, 5.19, and 8.94 for ADH (p<0.001), and 2.58, 3.49, and 4.97 for ALH (p=0.001). Conclusions In two independent cohort studies of benign breast disease, extent of atypia stratifies long-term breast cancer risk for ADH and ALH. PMID:27352219

Relationship between increasing concentrations of two carcinogens and statistical image descriptors of foci morphology in the cell transformation assay.

PubMed

Callegaro, Giulia; Corvi, Raffaella; Salovaara, Susan; Urani, Chiara; Stefanini, Federico M

2017-06-01

Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i.e. the step in which transformed colonies or foci are evaluated through morphological features. An objective evaluation of morphological features has been previously obtained through automated digital processing of foci images to extract the value of three statistical image descriptors. In this study a further potential of the CTA using BALB/c 3T3 cells is addressed by analysing the effect of increasing concentrations of two known carcinogens, benzo[a]pyrene and NiCl 2 , with different modes of action on foci morphology. The main result of our quantitative evaluation shows that the concentration of the considered carcinogens has an effect on foci morphology that is statistically significant for the mean of two among the three selected descriptors. Statistical significance also corresponds to visual relevance. The statistical analysis of variations in foci morphology due to concentration allowed to quantify morphological changes that can be visually appreciated but not precisely determined. Therefore, it has the potential of providing new quantitative parameters in CTAs, and of exploiting all the information encoded in foci. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Novel Image Processing Interface to Relate DSB Spatial Distribution from Immunofluorescence Foci Experiments to the State-of-the-Art Models of DNA Breakage

NASA Technical Reports Server (NTRS)

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.

Reliability of a Fully Automated Interpretation of γ -H2AX Foci in Lymphocytes of Moderately Trained Subjects under Resting Conditions.

PubMed

Heydenreich, Juliane; Otto, Christoph; Mayer, Frank; Carlsohn, Anja

2014-01-01

Background. Analysis of γ-H2AX foci is a promising approach to evaluate exercise-induced DNA damage. However, baseline levels and day-to-day variability of γ-H2AX foci have not been investigated in healthy subjects at rest. Methods. Blood was taken from eight moderately trained healthy males (29 ± 3 yrs, 1.84 ± 0.03 m, and 85 ± 6 kg) at two separate days (M1/M2) after 24-hour exercise cessation. Number of γ-H2AX foci per 100 lymphocytes (N), number of foci per affected lymphocyte (NAL), percentage of affected lymphocytes (PAL), and diameter (D) of γ-H2AX foci were analyzed (mean ± SD). Differences between M1 and M2 were analyzed using paired t-tests (α = 0.05). Day-to-day variability was evaluated by calculating the coefficients of variation (CV%), bias, and limits of agreement (LoA). Results. There were no statistically significant differences between M1 (N: 7.6 ± 4.4, NAL: 1.2 ± 0.2, PAL: 5.9 ± 2.6%, and D: 0.63 ± 0.07) and M2 (N: 8.4 ± 4.6, NAL: 1.3 ± 0.1, PAL: 6.9 ± 4.2%, and D: 0.66 ± 0.06). CV was calculated to be 98.5% (N), 88.9% (PAL), 11.3% (NAL), and 8.0% (D). Bias (LoA) was 0.75 (-15.2/13.7), -0.02 (-0.36/0.33), -1.0 (-11.9/9.9), and -0.04 (-0.16/0.09), respectively. Conclusions. Background level in healthy subjects is approximately 0.07 to 0.09 γ-H2AX foci/cell. NAL and D are reliable measures.

Induction and quantification of gammma-H2AX foci following cx- and gamma-irradiaton

NASA Technical Reports Server (NTRS)

Leatherbarrow, E. L.; Cucinotta, F. A.; O'Neill, Peter

2004-01-01

Following DNA damage the histone H2AX becomes phosphorylated and can be visualised by immunofluorescence as an indicator of DSBs in individual cells. Using a wild type hamster cell line (V79-4) exposed to either a-particles or to Co-60 gamma-rays to induce DNA DSBs at different doses (20-200OmGy), the dose dependent induction of gamma-H2AX foci were scored both manually (by eye) and using image analysis. A linearly dependence on dose was found for both radiations. The number of DSBs determined by image analysis after a post-irradiation period of 30 minutes at 37 C, is 16.6 foci/cell/Gy for alpha-irradiation and 12.2 foci/cell/Gy for gamma-irradiation; the latter being 3-4 times the levels observed by eye and comparable to gamma-radiation-induced levels of prompt DSBs more recently reported using pulse field gel electrophoresis (approx. 16 DSBs/Gy). The average size of the gamma-H2AX foci induced by alpha-irradiation (0.30 square micrometers) is approximately 1.5 times larger than those induced by gamma-irradiation (0.19 square micrometers). The timescale of induction and removal of DSBs up to 24 hours post-irradiation, was investigated with gamma-H2AX foci levels found to remain significantly higher than controls for 4 or 6 hours in gamma-irradiated samples or alpha irradiated samples, respectively. These results demonstrate that not only gamma radiation but also alpha-radiation induce phosphorylation of the H2AX histone in response to DSBs even at low doses (20mGy for gamma-rays, 1 track/cell on average for alpha-particles) and the variation in size and dephosphorylation of the induced foci is dependent on radiation quality (LET).

γH2AX assay in ex vivo irradiated tumour specimens: A novel method to determine tumour radiation sensitivity in patient-derived material.

PubMed

Menegakis, Apostolos; von Neubeck, Cläre; Yaromina, Ala; Thames, Howard; Hering, Sandra; Hennenlotter, Joerg; Scharpf, Marcus; Noell, Susan; Krause, Mechthild; Zips, Daniel; Baumann, Michael

2015-09-01

To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after >12h following ex vivo irradiation. Fitting the dose-response of residual γH2AX foci yielded slopes comparable with in situ irradiation of FaDu tumours. Significant differences in the slopes of ex vivo irradiated patient-derived tumour samples were found. A novel clinically applicable method to quantify residual γH2AX foci in ex vivo irradiated tumour samples was established. The first clinical results suggest that this method allows to distinguish between radiosensitive and radioresistant tumour types. These findings support further translational evaluation of this assay to individualise radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

PubMed

Persinger, Michael A

2009-01-01

To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

Multiple primary Ewing’s sarcomas in cerebral cranium of a child: a case report and review of the literature

PubMed Central

Wang, Dawei; Guo, Zongze

2015-01-01

Ewing’s sarcoma is the second most common pediatric bone tumor. Primary Ewing’s sarcoma occurring in the cerebral cranium is exceptionally rare, with only one reported case of multiple tumor lesions in adolescence to date. We report a case of a 5-year-old male patient with multiple primary Ewing’s sarcomas associated with the cranial bones, the first pediatric case report to date. We also review 71 cases Ewing’s sarcoma involving intracranial extension. The purpose of this article is to provide data concerning the clinical and therapeutic course of multiple primary Ewing’s sarcomas in associated with cerebral cranium. PMID:26261672

Reciprocal Interactions between Multiple Myeloma Cells and Osteoprogenitor Cells Affect Bone Formation and Tumor Growth

DTIC Science & Technology

2014-10-01

representation of the mechanism of affinity of Ald-PP NPs with bone mineral ( gray , bone mineral; red, Ald; green, PEG; yellow, PLGA). (C) Representative...8217-TCTGCCAGTCCCCCTAGAC-3’ MicroRNAs RNU6B 5’CGCAAGGATGACACGCAAATT-3’ ------------------ URP ------------------ 5’- GTG CAG GGT CCG AGG-3’ hsa-mir-199a

Characterization of Aes nuclear foci in colorectal cancer cells.

PubMed

Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M Mark

2016-01-01

Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Spatial distribution of earthquake hypocenters in the Crimea—Black Sea region

NASA Astrophysics Data System (ADS)

Burmin, V. Yu; Shumlianska, L. O.

2018-03-01

Some aspects of the seismicity the Crime—Black Sea region are considered on the basis of the catalogued data on earthquakes that have occurred between 1970 and 2012. The complete list of the Crimean earthquakes for this period contains about 2140 events with magnitude ranging from -1.5 to 5.5. Bulletins contain information about compressional and shear waves arrival times regarding nearly 2000 earthquakes. A new approach to the definition of the coordinates of all of the events was applied to re-establish the hypocenters of the catalogued earthquakes. The obtained results indicate that the bulk of the earthquakes' foci in the region are located in the crust. However, some 2.5% of the foci are located at the depths ranging from 50 to 250 km. The new distribution of foci of earthquakes shows the concentration of foci in the form of two inclined branches, the center of which is located under the Yalto-Alushta seismic focal zone. The whole distribution of foci in depth corresponds to the relief of the lithosphere.

Abutment Disconnection/Reconnection Affects Peri-implant Marginal Bone Levels: A Meta-Analysis.

PubMed

Koutouzis, Theofilos; Gholami, Fatemeh; Reynolds, John; Lundgren, Tord; Kotsakis, Georgios A

Preclinical and clinical studies have shown that marginal bone loss can be secondary to repeated disconnection and reconnection of abutments that affect the peri-implant mucosal seal. The aim of this systematic review and meta-analysis was to evaluate the impact of abutment disconnections/reconnections on peri-implant marginal bone level changes. To address this question, two reviewers independently performed an electronic search of three major databases up to October 2015 complemented by manual searches. Eligible articles were selected on the basis of prespecified inclusion and exclusion criteria after a two-phase search strategy and assessed for risk of bias. A random-effects meta-analysis was performed for marginal bone loss. The authors initially identified 392 titles and abstracts. After evaluation, seven controlled clinical studies were included. Qualitative assessment of the articles revealed a trend toward protective marginal bone level preservation for implants with final abutment placement (FAP) at the time of implant placement compared with implants for which there were multiple abutment placements (MAP). The FAP group exhibited a marginal bone level change ranging from 0.08 to 0.34 mm, whereas the MAP group exhibited a marginal bone level change ranging from 0.09 to 0.55 mm. Meta-analysis of the seven studies reporting on 396 implants showed significantly greater bone loss in cases of multiple abutment disconnections/reconnections. The weighted mean difference in marginal bone loss was 0.19 mm (95% confidence interval, 0.06-0.32 mm), favoring bone preservation in the FAP group. Within the limitations of this meta-analysis, abutment disconnection and reconnection significantly affected peri-implant marginal bone levels. These findings pave the way for revisiting current restorative protocols at the restorative treatment planning stage to prevent incipient marginal bone loss.

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

PubMed

Beckmann, Nicholas

2015-01-01

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.

Meeting report of the 2016 bone marrow adiposity meeting.

PubMed

van der Eerden, Bram; van Wijnen, André

2017-10-02

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

Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

PubMed Central

Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

1989-01-01

We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study.

PubMed

Schulze, Maximilian; Weisel, Katja; Grandjean, Caroline; Oehrlein, Katharina; Zago, Manola; Spira, Daniel; Horger, Marius

2014-01-01

The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy. From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category. Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4). Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome.

PubMed

Selvi, Subramanian Kalaivani; Kar, Rakhee; Vadivelan, Mehalingam; Subrahmanyam, Dharanipragada Krishna Suri

2012-01-01

Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.

Evaluating bone quality in patients with chronic kidney disease

PubMed Central

Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

2013-01-01

Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

[Current approaches in multiple myeloma and other cancer-related bone diseases].

PubMed

Engelhardt, M; Kleber, M; Udi, J; Wäsch, R

2012-05-01

Multiple myeloma (MM) ranges second of all hematological malignancies and occurs most commonly in elderly patients. Almost all MM patients develop bone lesions in the course of their disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, albeit computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly used as complementary techniques in the more sensitive detection of osteolytic processes. Bisphosphonates like zoledronate or pamidronate represent the cornerstone therapeutics in osteolytic disease, and are effective supportives to potent anti-myeloma therapies, including novel agents such as the proteasome inhibitor bortezomib or immunomodulatory drugs (IMIDs, e. g. thalidomide or lenalidomide). Several studies are ongoing to investigate the effects of alternative bone-seeking agents and their therapeutic potential for the management of myeloma bone disease, such as denosumab (RANKL-neutralizing antibody), anti-sclerostin (monoclonal antibody, generated against sclerostin) or sotatercept (potent activin-A inhibitor). This review summarizes the most prominent data on myeloma bone disease pathogenesis, the role of imaging techniques as well as therapy and prevention of lytic complications in myeloma which may similarly or equally be true for other bone metastases-inducing solid tumors. © Georg Thieme Verlag KG Stuttgart · New York.

The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays.

PubMed

Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong

2016-08-01

Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies.

Increased γ-H2A.X intensity in response to chronic medium-dose-rate γ-ray irradiation.

PubMed

Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

2012-01-01

The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G(1) phase, although no significant difference was observed in G(2)/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G(1) phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G(1) phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation.

Change in bone mineral density and its determinants in pre- and perimenopausal Chinese women: the Hong Kong Perimenopausal Women Osteoporosis Study.

PubMed

Ho, S C; Chan, S G; Yip, Y B; Chan, C S Y; Woo, J L F; Sham, A

2008-12-01

This 30-month study investigating bone change and its determinants in 438 perimenopausal Chinese women revealed that the fastest bone loss occurred in women undergoing menopausal transition but maintenance of body weight and physical fitness were beneficial for bone health. Soy protein intake also seemed to exert a protective effect. This 30-month follow-up study aims to investigate change in bone mineral density and its determinants in Hong Kong Chinese perimenopausal women. Four hundred and thirty-eight women aged 45 to 55 years were recruited through random telephone dialing and primary care clinic. Bone mass, body composition, lifestyle measurements were obtained at baseline and at 9-, 18- and 30-month follow-ups. Univariate and stepwise multiple regression analyses were performed with the regression coefficients of BMD/C (derived from baseline and follow-up measurements) as the outcome variables. Menopausal status was classified as pre- or postmenopausal or transitional. Menopausal status was the strongest determinant of bone changes. An annual bone loss of about 0.5% was observed among premenopausal, 2% to 2.5% among transitional, and about 1.5% in postmenopausal women. Multiple regression analyses, revealed that a positive regression slope of body weight was protective for follow-up bone loss at all sites. Number of pregnancy, soy protein intake and walking were protective for total body BMC. Higher baseline LM was also protective for neck of femur BMD. Maintenance of body weight and physical fitness were observed to have a protective effect on for bone loss in Chinese perimenopausal women.

Multiple myeloma in an Amur tiger (Panthera tigris altaica)

PubMed Central

Lee, Alison M.; Guppy, Naomi; Bainbridge, John; Jahns, Hanne

2017-01-01

The Amur tiger (Panthera tigris altaica) is an endangered tiger subspecies. An adult zoo-bred female was found collapsed, and died despite supportive treatment. Hematology and biochemistry showed pancytopenia and hyperglobulinemia, and serum protein electrophoresis revealed a monoclonal band in the β-globulin region. Necropsy demonstrated hemoabdomen, multifocal lytic bone marrow lesions, splenomegaly, and hemorrhagic hepatic nodules, with left medial lobe rupture. There were mutifocal hemorrhages in the subcutis, lung, epicardium, and intestinal mucosa. Histopathology demonstrated plasmacytoid cells infiltrating the bone marrow, liver and spleen, and circulating within blood vessels. On immunohistochemistry, cell infiltrates of the three tissues were positive for λ light chains, bone marrow infiltrates were positive for MUM-1 and bone marrow and spleen infiltrates were positive for CD20. These findings indicate that this animal died of hemoabdomen subsequent to multiple myeloma. This is the first time this disease has been reported in a tiger. PMID:29138744

Multiple myeloma in an Amur tiger (Panthera tigris altaica).

PubMed

Lee, Alison M; Guppy, Naomi; Bainbridge, John; Jahns, Hanne

2017-01-01

The Amur tiger ( Panthera tigris altaica ) is an endangered tiger subspecies. An adult zoo-bred female was found collapsed, and died despite supportive treatment. Hematology and biochemistry showed pancytopenia and hyperglobulinemia, and serum protein electrophoresis revealed a monoclonal band in the β-globulin region. Necropsy demonstrated hemoabdomen, multifocal lytic bone marrow lesions, splenomegaly, and hemorrhagic hepatic nodules, with left medial lobe rupture. There were mutifocal hemorrhages in the subcutis, lung, epicardium, and intestinal mucosa. Histopathology demonstrated plasmacytoid cells infiltrating the bone marrow, liver and spleen, and circulating within blood vessels. On immunohistochemistry, cell infiltrates of the three tissues were positive for λ light chains, bone marrow infiltrates were positive for MUM-1 and bone marrow and spleen infiltrates were positive for CD20. These findings indicate that this animal died of hemoabdomen subsequent to multiple myeloma. This is the first time this disease has been reported in a tiger.

Polarized Raman spectroscopy of bone tissue: watch the scattering

NASA Astrophysics Data System (ADS)

Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

2010-02-01

Polarized Raman spectroscopy is widely used in the study of molecular composition and orientation in synthetic and natural polymer systems. Here, we describe the use of Raman spectroscopy to extract quantitative orientation information from bone tissue. Bone tissue poses special challenges to the use of polarized Raman spectroscopy for measurement of orientation distribution functions because the tissue is turbid and birefringent. Multiple scattering in turbid media depolarizes light and is potentially a source of error. Using a Raman microprobe, we show that repeating the measurements with a series of objectives of differing numerical apertures can be used to assess the contributions of sample turbidity and depth of field to the calculated orientation distribution functions. With this test, an optic can be chosen to minimize the systematic errors introduced by multiple scattering events. With adequate knowledge of the optical properties of these bone tissues, we can determine if elastic light scattering affects the polarized Raman measurements.

Combined TRAF6 Targeting and Proteasome Blockade Has Anti-myeloma and Anti-Bone Resorptive Effects.

PubMed

Chen, Haiming; Li, Mingjie; Sanchez, Eric; Wang, Cathy S; Lee, Tiffany; Soof, Camilia M; Casas, Christian E; Cao, Jasmin; Xie, Colin; Udd, Kyle A; DeCorso, Kevin; Tang, George Y; Spektor, Tanya M; Berenson, James R

2017-05-01

TNF receptor-associated factor 6 (TRAF6) has been implicated in polyubiquitin-mediated IL1R/TLR signaling through activation of IκB kinase (IKK) to regulate the NF-κB and JNK signaling pathways. Here, TRAF6 protein was determined to be overexpressed in bone marrow mononuclear cells (BMMC) from patients with multiple myeloma. TRAF6 expression in BMMCs from patients with progressive disease is significantly elevated as compared with individuals in complete remission, with monoclonal gammopathy of undetermined significance, or healthy subjects. Furthermore, TRAF6 dominant-negative (TRAF6dn) peptides were constructed which specifically reduced TRAF6 signaling and activation of IKK. TRAF6 not only reduced cellular growth but also increased the apoptosis of multiple myeloma tumor cells in a concentration-dependent fashion. Because TRAF6 activates IKK through polyubiquitination, independent of its proteasome activity, a TRAF6dn peptide was combined with the proteasome inhibitors bortezomib or carfilzomib to treat multiple myeloma. Importantly, targeting of TRAF6 in the presence of proteasome inhibition enhanced anti-multiple myeloma effects and also decreased TLR/TRAF6/NF-κB-related signaling. Finally, TRAF6dn dose dependently inhibited osteoclast cell formation from CD14 + monocytes, induced with RANKL and mCSF , and markedly reduced bone resorption in dentin pits. In all, these data demonstrate that blocking TRAF6 signaling has anti-multiple myeloma effects and reduces bone loss. Implications: The ability to target TRAF6 signaling and associated pathways in multiple myeloma suggests a promising new therapeutic approach. Mol Cancer Res; 15(5); 598-609. ©2017 AACR . ©2017 American Association for Cancer Research.

Quality of Bone Healing: Perspectives and Assessment Techniques

DTIC Science & Technology

2014-01-01

connective tissue specialized for load bearing . Embryologically, the formation of bone occurs via two routes: intramembranous and endochondral ossification.1...primarily suited to load bearing with two distinct configurations: an inner, porous, cancellous architecture and an outer, denser, cortical bone...delineate the multiple functions served by the human skeleton and then evaluate techniques for clinical assessment. Mechanical load bearing and transduction

Takayasu's arteritis presenting with focal periostitis affecting two limbs.

PubMed

Kim, J E; Kolh, E M; Kim, D K

1998-12-31

Takayasu's arteritis (TA) is a vasculitis of large and medium sized arteries. Involvement of bone in TA is very rare. We report a case of young woman who presented with multiple painful bone lesions which were identified as periostitis with new bone formation associated with TA. Our case is unique in that bony involvement in TA could occur independent of vascular stenosis.

Ready to Use Tissue Construct for Military Bone & Cartilage Trauma

DTIC Science & Technology

2015-12-01

loss, bone loss, cartilage loss, stiffness, limping, pain , arthritis, and permanent disability, often requiring multiple reconstructive surgeries and...immediate, short-term and long-term consequences such as acute limb loss, bone loss, cartilage loss, stiffness, limping, pain , arthritis, and permanent...blast-injury. Osteochondral injuries of any size require anatomically perfect reconstruction to prevent pain and post-traumatic arthritis. We

Practical use of bone scan in patients with an osteoporotic vertebral compression fracture.

PubMed

Jun, Deuk Soo; An, Byoung Keun; Yu, Chang Hun; Hwang, Kyung Hoon; Paik, Je Won

2015-02-01

Rib fractures are one of main causes of chest or flank pain when related to an osteoporotic vertebral compression fracture (OVCF). The authors investigated the incidence and risk factors of rib fracture in 284 patients with OVCF using bone scans and evaluated the feasibility as to whether bone scans could be utilized as a useful screening tool. Hot uptake lesions on ribs were found in 122 cases (43.0%). The factors analyzed were age, sex, number and locations of fractured vertebrae, BMD, and compression rates as determined using initial radiography. However, no statistical significances were found. In 16 cases (5.6%), there were concurrent multiple fractures of both the thoracic and lumbar spines not detected by single site MRI. Sixty cases (21.1%) of OVCF with the a compression rate of less than 15% could not be identified definitely by initial plain radiography, but were confirmed by bone scans. It is concluded that a bone scan has outstanding ability for the screening of rib fractures associated with OVCF. Non-adjacent multiple fractures in both thoracic and lumbar spines and fractures not identified definitely by plain radiography were detected on bone scans, which provided a means for determining management strategies and predicting prognosis.

Quantitative polarized Raman spectroscopy in highly turbid bone tissue

NASA Astrophysics Data System (ADS)

Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

2010-05-01

Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

Quantitative polarized Raman spectroscopy in highly turbid bone tissue.

PubMed

Raghavan, Mekhala; Sahar, Nadder D; Wilson, Robert H; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H; Morris, Michael D

2010-01-01

Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

Peak bone strength is influenced by calcium intake in growing rats.

PubMed

Viguet-Carrin, S; Hoppler, M; Membrez Scalfo, F; Vuichoud, J; Vigo, M; Offord, E A; Ammann, P

2014-11-01

In this study we investigated the effect of supplementing the diet of the growing male rat with different levels of calcium (from low to higher than recommended intakes at constant Ca/P ratio), on multiple factors (bone mass, strength, size, geometry, material properties, turnover) influencing bone strength during the bone accrual period. Rats, age 28days were supplemented for 4weeks with high Ca (1.2%), adequate Ca (0.5%) or low Ca level (0.2%). Bone metabolism and structural parameters were measured. No changes in body weight or food intake were observed among the groups. As anticipated, compared to the adequate Ca intake, low-Ca intake had a detrimental impact on bone growth (33.63 vs. 33.68mm), bone strength (-19.7% for failure load), bone architecture (-58% for BV/TV) and peak bone mass accrual (-29% for BMD) due to the hormonal disruption implied in Ca metabolism. In contrast, novel, surprising results were observed in that higher than adequate Ca intake resulted in improved peak bone strength (106 vs. 184N/mm for the stiffness and 61 vs. 89N for the failure load) and bone material properties (467 vs. 514mPa for tissue hardness) but these effects were not accompanied by changes in bone mass, size, microarchitecture or bone turnover. Hormonal factors, IGF-I and bone modeling were also evaluated. Compared to the adequate level of Ca, IGF-I level was significantly lower in the low-Ca intake group and significantly higher in the high-Ca intake group. No detrimental effects of high Ca were observed on bone modeling (assessed by histomorphometry and bone markers), at least in this short-term intervention. In conclusion, the decrease in failure load in the low calcium group can be explained by the change in bone geometry and bone mass parameters. Thus, improvements in mechanical properties can be explained by the improved quality of intrinsic bone tissue as shown by nanoindentation. These results suggest that supplemental Ca may be beneficial for the attainment of peak bone strength and that multiple factors linked to bone mass and strength should be taken into account when setting dietary levels of adequate mineral intake to support optimal peak bone mass acquisition. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

PubMed

Fonti, R; Del Vecchio, S; Zannetti, A; De Renzo, A; Di Gennaro, F; Catalano, L; Califano, C; Pace, L; Rotoli, B; Salvatore, M

2001-02-01

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-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 99mTc-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 99mTc-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 99mTc-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 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-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 99mTc-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 compartments.

Hypoechoic foci on EUS are simple and strong predictive factors for neoplastic gallbladder polyps.

PubMed

Cho, Jae Hee; Park, Jeong Youp; Kim, Yoon Jae; Kim, Hee Man; Kim, Hong Jeong; Hong, Sung Pil; Park, Seung Woo; Chung, Jae Bock; Song, Si Young; Bang, Seungmin

2009-06-01

EUS is an accurate imaging modality for delineating gallbladder (GB) structures; however, its clinical use in differentiating neoplastic GB polyps from nonneoplastic polyps is limited. Thus, we sought to characterize neoplastic GB polyps by analyzing unique EUS features. Our analysis revealed variably shaped, relatively hypoechoic portions in the core of polyps compared with general background echogenicity. Our purpose was to make a differential diagnosis between neoplastic and nonneoplastic GB polyps of less than 20 mm by use of EUS variables, including hypoechoic foci. Retrospective single-center study. University teaching hospital. Patients (n = 88) underwent preoperative EUS and cholecystectomy for GB polyps smaller than 20 mm. Hypoechoic foci were found in 30 of 33 patients (91%) with neoplastic polyps and 6 of 55 (11%) with nonneoplastic polyps. In a multivariate analysis, hypoechoic foci were the only significant predictive factor for neoplastic polyps (odds ratio [OR] 55.4, 95% CI, 8.26-371, P < .001); the sensitivity and specificity were 90% and 89%, respectively. In addition, polyps >15 mm had an increased risk of malignancy (OR 21.7, 95% CI, 2.35-201, P = .007), as did those with hypoechoic foci (OR 10.9; 95% CI, 1.01-117, P = .049). Retrospective review of selected patients from a tertiary medical center. The presence of hypoechoic foci on EUS is a strong predictive factor for neoplastic polyps. EUS may be useful in developing a treatment strategy for GB polyps.

Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease.

PubMed

Soul, Janet S; Robertson, Richard L; Wypij, David; Bellinger, David C; Visconti, Karen J; du Plessis, Adré J; Kussman, Barry D; Scoppettuolo, Lisa A; Pigula, Frank; Jonas, Richard A; Newburger, Jane W

2009-08-01

Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury. Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age. Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%). Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy.

PubMed

Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kitano, Atsuko; Sasada, Shinsuke; Shimomura, Akihiko; Noguchi, Emi; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Fujiwara, Yasuhiro; Tamura, Kenji

2017-11-01

Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment.

Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy

PubMed Central

Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kitano, Atsuko; Sasada, Shinsuke; Shimomura, Akihiko; Noguchi, Emi; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Fujiwara, Yasuhiro; Tamura, Kenji

2017-01-01

Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment. PMID:28943574

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

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

Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh

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-relatedmore » 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.« less

Taylor spatial frame fixation in patients with multiple traumatic injuries: study of 57 long-bone fractures.

PubMed

Sala, Francesco; Elbatrawy, Yasser; Thabet, Ahmed M; Zayed, Mahmoud; Capitani, Dario

2013-08-01

To evaluate the Taylor spatial frame (TSF) for primary and definitive fixation of lower limb long-bone fractures in patients with multiple traumatic injuries. Retrospective. Level I trauma center. Consecutive series of 52 patients, 57 fractures (25 femoral and 32 tibial), treated between 2005 and 2009. Forty-nine fractures (86%) were open. Injury Severity Score ≥16 for all patients. Fifty-four fractures (95%) underwent definitive fixation with the TSF and 3 were treated primarily within 48 hours of injury. In 22 cases (39%), fractures were acutely reduced with the TSF, fixed to bone and the struts in sliding mode without further adjustment, and in 35 cases (61%), the total residual deformity correction program was undertaken. Clinical and radiological. Complete union was obtained in 52 fractures (91%) without additional surgery at an average of 29 weeks. Four nonunions and 1 delayed union occurred. Results based on Association for the Study and Application of the Method of Ilizarov criteria: 74% excellent, 16% good, 4% fair, and 7% poor for bone outcomes and 35% excellent, 47% good, and 18% fair for functional outcomes. Eighty-eight percent of patients returned to preinjury work activities. Primary and definitive fixation with the TSF is effective. Advantages include continuity of device until union, reduced risk of infection, early mobilization, restoration of primary defect caused by bone loss, easy and accurate application, convertibility and versatility compared with a monolateral fixator, and improved union rate and range of motion for lower extremity long-bone fractures in patients with multiple traumatic injuries.

Comparing diagnostic accuracy of bedside ultrasound and radiography for bone fracture screening in multiple trauma patients at the ED.

PubMed

Bolandparvaz, Shahram; Moharamzadeh, Payman; Jamali, Kazem; Pouraghaei, Mahboob; Fadaie, Maryam; Sefidbakht, Sepideh; Shahsavari, Kavous

2013-11-01

Long bone fractures are currently diagnosed using radiography, but radiography has some disadvantages (radiation and being time consuming). The present study compared the diagnostic accuracy of bedside ultrasound and radiography in multiple trauma patients at the emergency department (ED). The study assessed 80 injured patients with multiple trauma from February 2011 to July 2012. The patients were older than 18 years and triaged to the cardiopulmonary resuscitation ward of the ED. Bedside ultrasound and radiography were conducted for them. The findings were separately and blindly assessed by 2 radiologists. Sensitivity, specificity, the positive and negative predictive value, and κ coefficient were measured to assess the accuracy and validity of ultrasound as compared with radiography. The sensitivity of ultrasound for diagnosis of limb bone fractures was not high enough and ranged between 55% and 75% depending on the fracture site. The specificity of this diagnostic method had an acceptable range of 62% to 84%. Ultrasound negative prediction value was higher than other indices under study and ranged between 73% and 83%, but its positive prediction value varied between 33.3% and 71%. The κ coefficient for diagnosis of long bone fractures of upper limb (κ = 0.58) and upper limb joints (κ = 0.47) and long bones of lower limb (κ = 0.52) was within the medium range. However, the value for diagnosing fractures of lower limb joints (κ = 0.47) was relatively low. Bedside ultrasound is not a reliable method for diagnosing fractures of upper and lower limb bones compared with radiography. © 2013 Elsevier Inc. All rights reserved.

Meeting report of the 2016 bone marrow adiposity meeting

PubMed Central

van der Eerden, Bram; van Wijnen, André

2017-01-01

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

Activation of Wnt Signaling by Mechanical Loading Is Impaired in the Bone of Old Mice

PubMed Central

Holguin, Nilsson; Brodt, Michael D; Silva, Matthew J

2017-01-01

Aging diminishes bone formation engendered by mechanical loads, but the mechanism for this impairment remains unclear. Because Wnt signaling is required for optimal loading-induced bone formation, we hypothesized that aging impairs the load-induced activation of Wnt signaling. We analyzed dynamic histomorphometry of 5-month-old, 12-month-old, and 22-month-old C57Bl/6JN mice subjected to multiple days of tibial compression and corroborated an age-related decline in the periosteal loading response on day 5. Similarly, 1 day of loading increased periosteal and endocortical bone formation in young-adult (5-month-old) mice, but old (22-month-old) mice were unresponsive. These findings corroborated mRNA expression of genes related to bone formation and the Wnt pathway in tibias after loading. Multiple bouts (3 to 5 days) of loading upregulated bone formation–related genes, e.g., Osx and Col1a1, but older mice were significantly less responsive. Expression of Wnt negative regulators, Sost and Dkk1, was suppressed with a single day of loading in all mice, but suppression was sustained only in young-adult mice. Moreover, multiple days of loading repeatedly suppressed Sost and Dkk1 in young-adult, but not in old tibias. The age-dependent response to loading was further assessed by osteocyte staining for Sclerostin and LacZ in tibia of TOPGAL mice. After 1 day of loading, fewer osteocytes were Sclerostin-positive and, corroboratively, more osteocytes were LacZ-positive (Wnt active) in both 5-month-old and 12-month-old mice. However, although these changes were sustained after multiple days of loading in 5-month-old mice, they were not sustained in 12-month-old mice. Last, Wnt1 and Wnt7b were the most load-responsive of the 19 Wnt ligands. However, 4 hours after a single bout of loading, although their expression was upregulated threefold to 10-fold in young-adult mice, it was not altered in old mice. In conclusion, the reduced bone formation response of aged mice to loading may be due to failure to sustain Wnt activity with repeated loading. PMID:27357062

Denosumab for the management of bone disease in patients with solid tumors.

PubMed

Body, Jean-Jacques

2012-03-01

Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

Rise to SUMMIT: the Sydney University Multiple-Mirror Telescope

NASA Astrophysics Data System (ADS)

Moore, Anna M.; Davis, John

2000-07-01

The Sydney University Multiple Mirror Telescope (SUMMIT) is a medium-sized telescope designed specifically for high resolution stellar spectroscopy. Throughout the design emphasis has been placed on high efficiency at low cost. The telescope consists of four 0.46 m diameter mirrors mounted on a single welded steel frame. Specially designed mirror cells support and point each mirror, allowing accurate positioning of the images on optical fibers located at the foci of the mirrors. Four fibers convey the light to the future location of a high resolution spectrograph away from the telescope in a stable environment. An overview of the commissioning of the telescope is presented, including the guidance and automatic mirror alignment and focussing systems. SUMMIT is located alongside the Sydney University Stellar Interferometer at the Paul Wild Observatory, near Narrabri, Northern New South Wales.

Effects of the Inter-Parental Relationship on Adolescents’ Emotional Security and Adjustment: The Important Role of Fathers

PubMed Central

Suh, Go Woon; Fabricius, William V.; Stevenson, Matthew M.; Parke, Ross D.; Cookston, Jeffrey T.; Braver, Sanford L.; Saenz, Delia S.

2016-01-01

We examined the mediational roles of multiple types of adolescents’ emotional security in relations between multiple aspects of the inter-parental relationship and adolescents’ mental health from ages 13 to 16 (N = 392). General marital quality, non-violent parent conflict, and physical intimate partner violence independently predicted mental health. Security in the father-adolescent relationship, over and above security with the mother and security in regard to parent conflict, mediated the link from general marital quality to adolescents’ mental health. With two exceptions, paths were stable for boys and girls, biological- and step-fathers, and Anglo- and Mexican-Americans. The findings reveal the need to expand the traditional foci on parent conflict and relationships with mothers to include general marital quality and relationships with fathers. PMID:27690497

Effects of the interparental relationship on adolescents' emotional security and adjustment: The important role of fathers.

PubMed

Suh, Go Woon; Fabricius, William V; Stevenson, Matthew M; Parke, Ross D; Cookston, Jeffrey T; Braver, Sanford L; Saenz, Delia S

2016-10-01

We examined the mediational roles of multiple types of adolescents' emotional security in relations between multiple aspects of the interparental relationship and adolescents' mental health from ages 13 to 16 (N = 392). General marital quality, nonviolent parent conflict, and physical intimate partner violence independently predicted mental health. Security in the father-adolescent relationship, over and above security with the mother and security in regard to parent conflict, mediated the link from general marital quality to adolescents' mental health. With 2 exceptions, paths were stable for boys and girls, biological- and stepfathers, and Anglo- and Mexican Americans. The findings reveal the need to expand the traditional foci on parent conflict and relationships with mothers to include general marital quality and relationships with fathers. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Sprayable enzyme-activatable fluorescent probes: kinetic mapping using dynamic fluorescence imaging can help detecting tiny cancer foci (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kobayashi, Hisataka

2017-02-01

Optical fluorescence-guided imaging is increasingly used to guide surgery and endoscopic procedures. Sprayable enzyme-activatable probes are particularly useful because of high target-to-background ratios that increase sensitivity for tiny cancer foci. However, green fluorescent activatable probes suffers from interference from autofluorescence found in biological tissue. Dynamic imaging followed by the kinetic analysis could be detected local enzyme activity and used to differentiate specific fluorescence arising from an activated probe in a tumor from autofluorescence in background tissues especially when low concentrations of the dye are applied to detect tiny cancer foci. Serial fluorescence imaging was performed using various concentrations of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) which was sprayed on the peritoneal surface with tiny implants of SHIN3-dsRed ovarian cancer tumors. Temporal differences in signal between specific green fluorescence in cancer foci and non-specific autofluorescence in background tissue was measured and processed into three kinetic maps reflecting maximum fluorescence signal (MF), wash-in rate (WIR), and area under the curve (AUC), respectively. Especially at lower concentrations, kinetic maps derived from dynamic fluorescence imaging were clearly superior to unprocessed images for detection small cancer foci.

The Focinator v2-0 - Graphical Interface, Four Channels, Colocalization Analysis and Cell Phase Identification.

PubMed

Oeck, Sebastian; Malewicz, Nathalie M; Hurst, Sebastian; Al-Refae, Klaudia; Krysztofiak, Adam; Jendrossek, Verena

2017-07-01

The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci. The refined software is now even more user-friendly due to a graphical interface and further features. Thus, we included an R-script-based mode for automated image opening, file naming, progress monitoring and an error report. Consequently, the evaluation no longer required the attendance of the operator after initial parameter definition. Moreover, the Focinator v2-0 is now able to perform multi-channel analysis of four channels and evaluation of protein-protein colocalization by comparison of up to three foci channels. This enables for example the quantification of foci in cells of a specific cell cycle phase.

Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

PubMed Central

Lee, Youn-Bok; Chen, Han-Jou; Peres, João N.; Gomez-Deza, Jorge; Attig, Jan; Štalekar, 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.

2013-01-01

Summary 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. PMID:24290757

Local measurements of the diffusion constant in multiple scattering media: Application to human trabecular bone imaging

NASA Astrophysics Data System (ADS)

Aubry, Alexandre; Derode, Arnaud; Padilla, Frédéric

2008-03-01

We present local measurements of the diffusion constant for ultrasonic waves undergoing multiple scattering. The experimental setup uses a coherent array of programmable transducers. By achieving Gaussian beamforming at emission and reception, an array of virtual sources and receivers located in the near field is constructed. A matrix treatment is proposed to separate the incoherent intensity from the coherent backscattering peak. Local measurements of the diffusion constant D are then achieved. This technique is applied to a real case: a sample of human trabecular bone for which the ultrasonic characterization of multiple scattering is an issue.

Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

PubMed

Gauthé, Mathieu; Testart Dardel, Nathalie; Ruiz Santiago, Fernando; Ohnona, Jessica; Nataf, Valérie; Montravers, Françoise; Talbot, Jean-Noël

2018-03-12

To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe 1 -Tyr 3 -octreotide labelled with gallium-68 ( 68 Ga-DOTA-TOC). In 535 NET patients, 68 Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUV max ) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm 3 , SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68 Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. The high sensitivity of 68 Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68 Ga-DOTA-TOC uptake. • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

Clinical Considerations of Adapted Drilling Protocol by Bone Quality Perception.

PubMed

Toia, Marco; Stocchero, Michele; Cecchinato, Francesca; Corrà, Enrico; Jimbo, Ryo; Cecchinato, Denis

To evaluate insertion torque value (ITV) and marginal bone loss (MBL) of an implant system after a clinically perceived bone quality-adapted drilling. This multicenter retrospective study included patients treated with implants, conventionally loaded, in completely healed sites. Operators customized the osteotomy preparation according to radiographic assessment and their perception of bone quality. Drilling sequence, bone quality, and ITV were recorded at the time of surgery. Radiographs were taken at the time of implant placement and permanent restoration. MBL between implant placement and permanent restoration was calculated. The implant was used as the statistical unit. Demographic and implant characteristics were shown by means of descriptive statistics. Outcome values were compared using analysis of variance (ANOVA) and Kruskal-Wallis tests. Multiple regression models were used to test the effect of independent variables on ITV and MBL. One hundred eighty-eight implants placed in 87 patients were included in the analysis. The mean observation period was 144 ± 59 days. The mean ITV was 30.8 ± 15.1 Ncm. ITV differed significantly based on arches (mandible/maxilla) (P = .001), bone quality (P < .001), implant diameter (P = .032), and drilling protocol (P = .019). Median MBL was 0.05 mm (0.00; 0.24). A significant difference was found between the mandible and maxilla (P = .008) and between drilling protocols (P = .011). In particular, significantly higher MBL was found in the undersized drilling protocol. Multiple regression analysis showed that ITV was influenced by bone quality and implant diameter. MBL was influenced by bone quality, implant diameter, ITV, and the interaction between bone quality and ITV. It was estimated that MBL was greater with increased bone density and ITV. Excessive ITV in dense bone can cause negative marginal bone responses. A presurgical radiographic assessment and the perception of bone quality are necessary to select an optimal drilling protocol and to minimize surgical trauma.

Adhesive interactions of human multiple myeloma cell lines with different extracellular matrix molecules.

PubMed

Kibler, C; Schermutzki, F; Waller, H D; Timpl, R; Müller, C A; Klein, G

1998-06-01

Multiple myeloma represents a human B cell malignancy which is characterized by a predominant localization of the malignant cell clone within the bone marrow. With the exception of the terminal stage of the disease the myeloma tumor cells do not circulate in the peripheral blood. The bone marrow microenvironment is believed to play an important role in homing, proliferation and terminal differentiation of myeloma cells. Here we have studied the expression of several extracellular matrix (ECM) molecules in the bone marrow of multiple myeloma patients and analyzed their adhesive capacities with four different human myeloma-derived cell lines. All ECM molecules analyzed (tenascin, laminin, fibronectin, collagen types I, III, V and VI) could be detected in bone marrow cryostat sections of multiple myeloma patients. Adhesion assays showed that only laminin, the microfibrillar collagen type VI and fibronectin were strong adhesive components for the myeloma cell lines U266, IM-9, OPM-2 and NCI-H929. Tenascin and collagen type I were only weak adhesive substrates for these myeloma cells. Adhesion to laminin and fibronectin was beta 1-integrin-mediated since addition of anti-beta 1-integrin antibodies could inhibit the binding of the four different cell types to both matrix molecules. In contrast, integrins do not seem to be involved in binding of the myeloma cells to collagen type VI. Instead, inhibition of binding by heparin suggested that membrane-bound heparan sulfate proteoglycans are responsible ligands for binding to collagen type VI. Adhesion assays with several B-cell lines resembling earlier differentiation stages revealed only weak interactions with tenascin and no interactions with collagen type VI, laminin or fibronectin. In summary, the interactions of human myeloma cells with the extracellular matrix may explain the specific retention of the plasma cells within the bone marrow.

The generalized mean zone plate

NASA Astrophysics Data System (ADS)

Xia, Tian; Cheng, Shubo; Tao, Shaohua

2018-06-01

In this paper a generalized mean zone plate is proposed, which generates twin foci located at the positions satisfying the expression of the generalized mean, which includes the m-golden mean, precious mean, and so on. The generalized mean zone plate can be designed to generate twin foci with various position ratios. The diffraction properties of the generalized mean zone plates have been investigated with simulations and experiments. The results show that the ratio of the positions of the twin foci for the generalized mean zone plate can be designed with the selected zone plate parameters.

[A case of multiple cavernous angioma with dementia].

PubMed

Kariya, S; Kawahara, M; Suzumura, A

2000-10-01

We reported a 65-year-old man who developed dementia since 50 years of age. His consciousness was clear but he was indifferent to his illness. Also, the luck of attention was recognized when we underwent examinations and the result of intellectual test varied every time we performed. His memory function was almost normal on the examination which was performed when he was cooperative. Magnetic resonance imaging (MRI) disclosed multiple tiny lesions (more than 130 in all) in cerebrum, brainstem, cerebellum and spinal cord. These lesions were compatible with multiple cavernous angioma. Most of lesions manifested high-density area on cranial CT. Though the multiplicity of foci indicated the possibility of familial occurrence, he was considered to be a sporadic case on his lineage investigation and the brain MRI of his only son. In this case, neither headache nor seizures which were known as the major clinical features of intracerebral cavernous angioma was observed. He was diagnosed as having white matter dementia characterized by attentional dysfunction, decrement of volition and less memory disturbance. We speculated that he developed symptomatic dementia by the sum of multiple minor degeneration, especially in frontal lobe white matter, caused by repeated minor bleeding from cavernous angiomas.

SPECT/CT in patients with lower back pain after lumbar fusion surgery.

PubMed

Sumer, Johannes; Schmidt, Daniela; Ritt, Philipp; Lell, Michael; Forst, Raimund; Kuwert, Torsten; Richter, Richard

2013-10-01

The aim of the study was to investigate the incremental diagnostic value of skeletal hybrid imaging with single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) over conventional nuclear medical imaging in patients with lower back pain after lumbar fusion surgery (LFS). This retrospective study comprised 37 patients suffering from lower back pain after LFS in whom three-phase planar bone scintigraphies of the lumbar spine including SPECT/CT of that region had been performed. The findings visible on these imaging data sets were classified into the following five diagnostic categories: (a) metal loosening; (b) insufficient stabilizing function of the metal implants indicated by metabolically active facet joint arthritis and/or intervertebral osteochondrosis in the instrumented region; (c) adjacent instability defined as metabolically active degenerative disease in the segments adjacent to the instrumented region; (d) indeterminate; and (e) normal. In the case of eight patients no lesions were visible on their planar scintigraphy and SPECT (planar/SPECT) or SPECT/CT images. In the remaining 29 patients, planar/SPECT disclosed 62 pathological foci of uptake within the graft region and SPECT/CT revealed 55. The rate of reclassification by SPECT/CT compared with planar/SPECT was 5/12 for lesions categorized as metal loosening by planar/SPECT, 16/29 for foci with a planar/SPECT diagnosis of insufficient stabilizing function, 7/20 when the planar/SPECT diagnosis had been adjacent instability, and 1/1 for the lesions indeterminate on planar/SPECT. Two lesions had been detected on SPECT/CT only. The overall rate of reclassification was 45.2% (28/62) (95% confidence interval, 33.4-57.5%). Because of its significantly higher accuracy compared with planar/SPECT, SPECT/CT should be the conventional nuclear medical procedure of choice for patients with lower back pain after LFS.

The Use of the Roentgen Ray by the Medical Department of the United States Army in the War with Spain (1898)

DTIC Science & Technology

1900-01-01

scientific value by showing the character of the bone lesions, the form of fracture, and the amount of bone comminution produced by the small-caliber and...without increasing its value. As the scientific value of the plates depends upon their being true representations of the objects as shown by the Rintgen...is adopted, and in such cases one of the metthods of localization by multiple observation must be resorted to. LOCALIZATION BY MULTIPLE OBSERVATION

Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies.

PubMed

Collins, Laura C; Aroner, Sarah A; Connolly, James L; Colditz, Graham A; Schnitt, Stuart J; Tamimi, Rulla M

2016-02-15

Women with atypical hyperplasia (AH) on a benign breast biopsy specimen are at increased risk for the development of breast cancer. However, the relation between the type and extent of AH (atypical ductal hyperplasia [ADH] vs atypical lobular hyperplasia [ALH]) and the magnitude of the breast cancer risk is not well defined. A nested case-control study of benign breast disease and breast cancer risk was conducted. Women with breast cancer and prior benign breast biopsy findings (488 cases) were matched to women with prior benign breast biopsy findings who were free from breast cancer (1907 controls). Benign breast biopsy slides were reviewed and categorized as nonproliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Among women with ADH, the interrelation between the extent of atypia and breast cancer risk was not significant (odds ratio [OR] for 1 or 2 foci, 3.5; 95% confidence interval [CI], 2.2-5.6; OR for ≥3 foci, 2.7; 95% CI, 1.4-5.1; P = .41). Similarly, although the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR for 1 or 2 foci, 5.2; 95% CI, 2.7-10.0; OR for ≥3 foci, 8.0; 95% CI, 4.5-14.2; P = .19). This analysis demonstrates that the extent of ADH or ALH does not significantly contribute to breast cancer risk. The lack of a significant dose-response relation between the extent and type of atypia and breast cancer risk suggests that it would be premature to use the extent of atypia to influence management decisions for women with ADH or ALH. © 2015 American Cancer Society.

Acute pyelonephritis in transplanted kidneys: can diffusion-weighted magnetic resonance imaging be useful for diagnosis and follow-up?

PubMed

Faletti, Riccardo; Cassinis, Maria Carla; Gatti, Marco; Giglio, Jacopo; Guarnaccia, Carla; Messina, Marina; Bergamasco, Laura; Fonio, Paolo

2016-03-01

To assess reliability of diffusion-weighted magnetic resonance imaging (DW-MRI) in the management of acute pyelonephritis (APN) foci in transplanted kidneys. In the 2012-2014 period, 24 kidney-transplanted patients underwent MR screening for clinical suspicion of APN. Two readers independently analyzed all images, establishing presence and location of APN foci. The 22 patients who were positive at the MR exam constituted the study population. For each patient the apparent diffusion coefficient (ADC) was measured in the APN foci and in three sites of the healthy parenchyma (case-control comparison). The data were matched to the laboratory measurements for white blood cell, C-reactive protein, and serum creatinine. Forty-six APN foci were found in 22/24 patients. At the acute stage, the difference in ADC between healthy parenchyma and APN foci was significant (2.06 ± 0.16 vs. 1.43 ± 0.32 × 10(-3) mm(2)/s; p < 0.0001). The performance of ADC as APN indicator was tested by the receiving operating characteristics (ROC) curve: the area under curve AUC = 0.99 witnessed an excellent discriminatory ability, with threshold APN/normal parenchyma 1.9 × 10(-3) mm(2)/s. At the 1-month follow-up 43/46 APN foci were no longer visible, with ADC values significantly higher than at the acute stage; all laboratory data were physiological, with WBC significantly reduced from the acute phase (5.2 ± 1.6 × 10(9)/L vs. 10.6 ± 4.8 × 10(9)/L; p < 0.0001). The other 3 patients underwent further therapy and exams, including a third MR. DW-MRI with ADC measurement seems to be a reliable tool in diagnosing and monitoring APN foci in transplanted kidneys, with clinical impact on patient management.

Development of a bone-fixation prosthetic attachment. [with quick-disconnect coupling

NASA Technical Reports Server (NTRS)

Owens, L. J.

1975-01-01

An artificial limb attached directly to the bone by a quick-disconnect coupling was tested in-place at a California medical rehabilitation center. Its design concept and development, made possible by multiple spinoffs of aerospace technology, are discussed.

Injection of demineralized bone matrix with bone marrow concentrate improves healing in unicameral bone cyst.

PubMed

Di Bella, Claudia; Dozza, Barbara; Frisoni, Tommaso; Cevolani, Luca; Donati, Davide

2010-11-01

Unicameral bone cysts are benign lesions that usually spontaneously regress with skeletal maturity; however, the high risk of pathologic fractures often justifies treatment that could reinforce a weakened bone cortex. Various treatments have been proposed but there is no consensus regarding the best procedure. We compared the healing rates and failures of two methods of cure based on multiple injections of corticosteroid or a single injection of demineralized bone matrix (DBM) in association with bone marrow concentrate (BMC). We retrospectively reviewed 184 patients who had one of the two treatments for unicameral bone cysts with cortical erosion. Clinical records were reviewed for treatment failures and radiographs for healing in all patients. The minimum followup was 12 months for the Steroids Group (mean, 48 months; range, 12-120 months) and 12 months for the DBM + BMC Group (mean, 20 months; range, 12-28 months). After one treatment we observed a lower healing rate of cysts treated with multiple injections of steroids compared with the healing after the first injection of DBM + BMC (21% versus 58%, respectively). At last followup, 38% healed with steroids and 71% with DBM + BMC. The rate of failure after one steroid injection was higher than after a single injection of BDM + BMC (63% versus 24%, respectively). We observed no difference in fracture rates after treatment between the two groups. A single injection of DBM added with autologous bone marrow concentrate appears to provide a higher healing rate with a lower number of failures compared with a single injection of steroids.

In Silico Investigations of the Anti-Catabolic Effects of Pamidronate and Denosumab on Multiple Myeloma-Induced Bone Disease

PubMed Central

Wang, Yan; Lin, Bo

2012-01-01

It is unclear whether the new anti-catabolic agent denosumab represents a viable alternative to the widely used anti-catabolic agent pamidronate in the treatment of Multiple Myeloma (MM)-induced bone disease. This lack of clarity primarily stems from the lack of sufficient clinical investigations, which are costly and time consuming. However, in silico investigations require less time and expense, suggesting that they may be a useful complement to traditional clinical investigations. In this paper, we aim to (i) develop integrated computational models that are suitable for investigating the effects of pamidronate and denosumab on MM-induced bone disease and (ii) evaluate the responses to pamidronate and denosumab treatments using these integrated models. To achieve these goals, pharmacokinetic models of pamidronate and denosumab are first developed and then calibrated and validated using different clinical datasets. Next, the integrated computational models are developed by incorporating the simulated transient concentrations of pamidronate and denosumab and simulations of their actions on the MM-bone compartment into the previously proposed MM-bone model. These integrated models are further calibrated and validated by different clinical datasets so that they are suitable to be applied to investigate the responses to the pamidronate and denosumab treatments. Finally, these responses are evaluated by quantifying the bone volume, bone turnover, and MM-cell density. This evaluation identifies four denosumab regimes that potentially produce an overall improved bone-related response compared with the recommended pamidronate regime. This in silico investigation supports the idea that denosumab represents an appropriate alternative to pamidronate in the treatment of MM-induced bone disease. PMID:23028650

β₂ adrenergic receptor activation suppresses bone morphogenetic protein (BMP)-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells.

PubMed

Yamada, Takayuki; Ezura, Yoichi; Hayata, Tadayoshi; Moriya, Shuichi; Shirakawa, Jumpei; Notomi, Takuya; Arayal, Smriti; Kawasaki, Makiri; Izu, Yayoi; Harada, Kiyoshi; Noda, Masaki

2015-06-01

β adrenergic stimulation suppresses bone formation in vivo while its actions in osteoblastic differentiation are still incompletely understood. We therefore examined the effects of β2 adrenergic stimulation on osteoblast-like MC3T3-E1 cells focusing on BMP-induced alkaline phosphatase expression. Morphologically, isoproterenol treatment suppresses BMP-induced increase in the numbers of alkaline phosphatase-positive small foci in the cultures of MC3T3-E1 cells. Biochemically, isoproterenol treatment suppresses BMP-induced enzymatic activity of alkaline phosphatase in a dose-dependent manner. Isoproterenol suppression of alkaline phosphatase activity is observed even when the cells are treated with high concentrations of BMP. With respect to cell density, isoproterenol treatment tends to suppress BMP-induced increase in alkaline phosphatase expression more in osteoblasts cultured at higher cell density. In terms of treatment protocol, continuous isoproterenol treatment is compared to cyclic treatment. Continuous isoproterenol treatment is more suppressive against BMP-induced increase in alkaline phosphatase expression than cyclic regimen. At molecular level, isoproterenol treatment suppresses BMP-induced enhancement of alkaline phosphatase mRNA expression. Regarding the mode of isoproterenol action, isoproterenol suppresses BMP-induced BRE-luciferase activity. These data indicate that isoproterenol regulates BMP-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells. © 2014 Wiley Periodicals, Inc.

Solitary Bone Plasmacytoma Progressing into Retroperitoneal Plasma Cell Myeloma with No Related End Organ or Tissue Impairment: A Case Report and Review of the Literature

PubMed Central

Tikku, Gargi; Jain, Monica; Mridha, Asit; Grover, Rajesh

2014-01-01

Solitary bone plasmacytomas and plasma cell myeloma are clonal proliferations of plasma cells. Many patients with solitary bone plasmacytomas develop plasma cell myeloma on follow-up. We present a case of a 70-year-old man who presented with fracture and a lytic lesion in the subtrochanteric region of the left femur and was assigned a diagnosis of solitary bone plasmacytoma. He received local curative radiotherapy. However, 4 months later his serum M protein and β2-microglobulin levels increased to 2.31 g/dL and 5.965 mg/L, respectively. He complained of abdominal fullness and constipation. Ultrasound and non-contrast CT imaging revealed multiple retroperitoneal masses. Colonoscopic examination was normal. Biopsy of the a retroperitoneal mass confirmed it to be a plasmacytoma. Repeat hemogram, blood urea, serum creatinine, skeletal survey, and bone marrow examination revealed no abnormalities. This is an unusual presentation of plasma cell myeloma, which manifested as multiple huge extramedullary retroperitoneal masses and arose from a solitary bone plasmacytoma, without related end organ or tissue impairment and bone marrow plasmacytosis. The patient succumbed to his disease 8 months after the appearance of the retroperitoneal masses. This case highlights the importance of close monitoring of patients diagnosed with solitary bone plasmacytoma with increased serum M protein and serum β2-microglobulin levels, so that early therapy can be instituted to prevent conversion to plasma cell myeloma. PMID:25330522

Comparison of methodologies in determining bone marrow fat percentage under different environmental conditions.

PubMed

Murden, David; Hunnam, Jaimie; De Groef, Bert; Rawlin, Grant; McCowan, Christina

2017-01-01

The use of bone marrow fat percentage has been recommended in assessing body condition at the time of death in wild and domestic ruminants, but few studies have looked at the effects of time and exposure on animal bone marrow. We investigated the utility of bone marrow fat extraction as a tool for establishing antemortem body condition in postmortem specimens from sheep and cattle, particularly after exposure to high heat, and compared different techniques of fat extraction for this purpose. Femora were collected from healthy and "skinny" sheep and cattle. The bones were either frozen or subjected to 40°C heat; heated bones were either wrapped in plastic to minimize desiccation or were left unwrapped. Marrow fat percentage was determined at different time intervals by oven-drying, or by solvent extraction using hexane in manual equipment or a Soxhlet apparatus. Extraction was performed, where possible, on both wet and dried tissue. Multiple samples were tested from each bone. Bone marrow fat analysis using a manual, hexane-based extraction technique was found to be a moderately sensitive method of assessing antemortem body condition of cattle up to 6 d after death. Multiple replicates should be analyzed where possible. Samples from "skinny" sheep showed a different response to heat from those of "healthy" sheep; "skinny" samples were so reduced in quantity by day 6 (the first sampling day) that no individual testing could be performed. Further work is required to understand the response of sheep marrow.

Adipose, Bone and Myeloma: Contributions from the Microenvironment

PubMed Central

McDonald, Michelle; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R.

2017-01-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide [1]. Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90% of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies. PMID:27343063

Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET-CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion.

PubMed

Ranade, Rohit; Basu, Sandip

2017-01-01

Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET.

Association with replication between estrogen-related receptor gamma (ESRRgamma) polymorphisms and bone phenotypes in women of European ancestry.

PubMed

Elfassihi, Latifa; Giroux, Sylvie; Bureau, Alexandre; Laflamme, Nathalie; Cole, David Ec; Rousseau, François

2010-04-01

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor gamma (ESRRgamma) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRgamma sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRgamma in the determination of bone density in women. Copyright 2010 American Society for Bone and Mineral Research.

Plague Outbreak in Libya, 2009, Unrelated to Plague in Algeria

PubMed Central

Cabanel, Nicolas; Leclercq, Alexandre; Chenal-Francisque, Viviane; Annajar, Badereddin; Rajerison, Minoarisoa; Bekkhoucha, Souad; Bertherat, Eric

2013-01-01

After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci. PMID:23347743

Understanding the Persistence of Plague Foci in Madagascar

PubMed Central

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

Plague outbreak in Libya, 2009, unrelated to plague in Algeria.

PubMed

Cabanel, Nicolas; Leclercq, Alexandre; Chenal-Francisque, Viviane; Annajar, Badereddin; Rajerison, Minoarisoa; Bekkhoucha, Souad; Bertherat, Eric; Carniel, Elisabeth

2013-02-01

After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci.

Understanding the persistence of plague foci in Madagascar.

PubMed

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.

Muscle-Bone Interactions in Pediatric Bone Diseases.

PubMed

Veilleux, Louis-Nicolas; Rauch, Frank

2017-10-01

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

PubMed

Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H

2003-02-01

Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune-competent Host--End Organ Damage from Head to Bone.

PubMed

Torres-Miranda, Daisy; Al-Saffar, Farah; Ibrahim, Saif; Font-Diaz, Stephanie

2015-01-01

This report describes a 64-years-old male patient that presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Spine CT failed to demonstrate any infectious foci but showed partially visualized lung cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin-sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed no signs of infective endocarditis (IE). Later, the patient experienced an acute deterioration on clinical status and examination showed development of a new murmur. He also developed new hemiparesis with up-going babinski reflex. A head MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1. Cerebro-spinal fluid was positive for meningitis. A transesophageal echocardiogram (TEE) was performed demonstrating new severe mitral and mild tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior mitral leaflet. We present is a very interesting case of a rapidly progressive MSSA infection. MSSA meningitis is a rare disease; there are only few reported cases in the literature to date. We describe a case of MSSA bacteremia, of questionable source, that resulted in MSSA endocarditis affecting right and left heart in a patient who did not have a history of intravenous drug use (IVDU) or immunosuppression. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and brain with consequent meningitis and stroke. Even when MSSA infections are well known, to our knowledge there are no previous case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. These latter are rarely reported, even individually.

Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study.

PubMed

Zhang, Jing; Li, Tingting; Xu, Liangzhi; Li, Wenjuan; Cheng, Meng; Zhuang, Jing; Chen, Yan; Xu, Wenming

2013-08-01

Leptin may be a potential option in preventing osteoporosis for menopausal women. The objective of this study is to explore the molecular mechanism of leptin on bone metabolism in osteoblast. Primary osteoblasts were isolated from parietal bone of adult female rats. mRNA level of OB-Rb in osteoblasts was inhibited by siRNA to block leptin signal transmission. The whole genome expression was tested by using gene chip to preliminarily explore the molecular mechanism of leptin in regulating osteoblast activity. The optimal concentration of siRNA was 25 nM, resulting in a maximal inhibition of OB-Rb mRNA. Ossification (p < 0.05) and bone mineralization (p = 0.0001) were downregulated by inhibiting leptin signal transmission, while bone resorption (p = 0.007), osteoblast differentiation (p = 0.026) and negative regulation of bone remodeling (p = 0.004) were upregulated. The expressions of some genes were regulated by OB-Rb siRNA. The expressions of alkaline phosphatase (p = 0.014) and osteocalcin (p = 0.002) were reduced, while that of vascular endothelial growth factor A (p = 0.0076) and IL-6 (p = 0.021) were increased. In a model of osteoblast, leptin positively promotes ossification through multiple ways including bone mineralization, remodeling, resorption and osteoblast differentiation, but which way plays the most critical role is not discussed in this study and needs to be clarified in future.

Validation of multiple subject-specific finite element models of unicompartmental knee replacement.

PubMed

Tuncer, Mahmut; Cobb, Justin P; Hansen, Ulrich N; Amis, Andrew A

2013-10-01

Accurate computer modelling of the fixation of unicompartmental knee replacements (UKRs) is a valuable design tool. However, models must be validated with in vitro mechanical tests to have confidence in the results. Ten fresh-frozen cadaveric knees with differing bone densities were CT-scanned to obtain geometry and bone density data, then implanted with cementless medial Oxford UKRs by an orthopaedic surgeon. Five strain gauge rosettes were attached to the tibia and femur of each knee and the bone constructs were mechanically tested. They were re-tested following implanting the cemented versions of the implants. Finite element models of four UKR tibiae and femora were developed. Sensitivity assessments and convergence studies were conducted to optimise modelling parameters. The cemented UKR pooled R(2) values for predicted versus measured bone strains were 0.85 and 0.92 for the tibia and femur respectively. The cementless UKR pooled R(2) values were slightly lower at 0.62 and 0.73 which may have been due to the irregularity of bone resections. The correlation of the results was attributed partly to the improved material property prediction method used in this project. This study is the first to validate multiple UKR tibiae and femora for bone strain across a range of specimen bone densities. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Genomic Surveillance Elucidates Persistent Wild Poliovirus Transmission During 2013-2015 in Major Reservoir Areas of Pakistan.

PubMed

Alam, Muhammad Masroor; Sharif, Salmaan; Shaukat, Shahzad; Angez, Mehar; Khurshid, Adnan; Rehman, Lubna; Zaidi, Syed Sohail Zahoor

2016-01-15

Despite tremendous efforts in the fight against polio, Pakistan bears the highest proportion of poliomyelitis cases among the 3 endemic countries including Afghanistan and Nigeria. Apart from insecurity and inaccessibility challenges, the substantial shift of unimmunized children from North Waziristan due to recent military operations was presumed to favor the widespread poliovirus infection in Pakistan. To better understand the current epidemiological situation, we analyzed the virologic data of wild poliovirus type 1 (WPV1) strains detected in Pakistan during 2013-2015. Five genetic clusters (A-E) were identified with at least 5% nucleotide divergence in the viral protein 1 (VP1) coding region. Peshawar, Quetta, and Karachi were found to be the major endemic foci where multiple discrete genetic lineages of WPV1 were detected. Phylogenetic analysis suggests that wild poliovirus strains from endemic regions were genetically distant (with 5%-15% VP1 nucleotide divergence) from those detected in North Waziristan cases, excluding the possibility of a recent progenitor of WPV1 instigating single-source transmission across the country. Orphan lineages detected in Rawalpindi, Lahore, Hyderabad, Sukkur, and Jacobabad revealed silent transmission and the need for vigilant surveillance. Sustenance of analogous genetic lineages over a period of 3 years highlights multiple unimmunized foci present to maintain viral genetic diversity. Our findings are inconsistent with the hypothesis that impoverished populations from North Waziristan serve as a possible determinant of widespread poliomyelitis infection in Pakistan and further emphasize the need to scale-up clinical and environmental surveillance as well as immunization activities. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Inhibition of exportin-1 function results in rapid cell cycle-associated DNA damage in cancer cells

PubMed Central

Burke, Russell T.; Marcus, Joshua M.; Orth, James D.

2017-01-01

Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE. In multiple cell models, selinexor treatment results in the formation of clustered DNA damage foci in 30-40% of cells within 8 hours that is dependent upon cysteine-528. DNA damage strongly correlates with G1/S-phase and decreased DNA replication. Live cell microscopy reveals an association between DNA damage and cell fate. Cells that form damage in G1-phase more often die or arrest, while those damaged in S/G2-phase frequently progress to cell division. Up to half of all treated cells form damage foci, and most cells that die after being damaged, were damaged in G1-phase. By comparison, non-transformed cell lines show strong cell cycle effects but little DNA damage and less death than cancer cells. Significant drug combination effects occur when selinexor is paired with different classes of agents that either cause DNA damage or that diminish DNA damage repair. These data present a novel effect of exportin-1 inhibition and provide a strong rationale for multiple combination treatments of selinexor with agents that are currently in use for the treatment of different solid cancers. PMID:28467801

Age-associated bone loss and intraskeletal variability in the Imperial Romans.

PubMed

Cho, Helen; Stout, Sam Darrel

2011-01-01

An Imperial Roman sample from the Isola Sacra necropolis (100-300 A.D.) offered an opportunity to histologically examine bone loss and intraskeletal variability in an urban archaeological population. Rib and femur samples were analyzed for static indices of bone remodeling and measures of bone mass. The Imperial Romans experienced normal age-associated bone loss via increased intracortical porosity and endosteal expansion, with females exhibiting greater bone loss and bone turnover rates than in males. Life events such as menopause and lactation coupled with cultural attitudes and practices regarding gender and food may have led to increased bone loss in females. Remodeling dynamics differ between the rib and femur and the higher remodeling rates in the rib may be attributed to different effective age of the adult compacta or loading environment. This study demonstrates that combining multiple methodologies to examine bone loss is necessary to shed light on the biocultural factors that influence bone mass and bone loss.

Effects of Condensation on Peri-implant Bone Density and Remodeling

PubMed Central

Wang, L.; Wu, Y.; Perez, K.C.; Hyman, S.; Brunski, J.B.; Tulu, U.; Bao, C.; Salmon, B.; Helms, J.A.

2017-01-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability. PMID:28048963

Effects of Condensation on Peri-implant Bone Density and Remodeling.

PubMed

Wang, L; Wu, Y; Perez, K C; Hyman, S; Brunski, J B; Tulu, U; Bao, C; Salmon, B; Helms, J A

2017-04-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability.

Subtle Hemorrhagic Brain Injury is Associated with Neurodevelopmental Impairment in Infants with Repaired Congenital Heart Disease

PubMed Central

Soul, Janet S.; Robertson, Richard L.; Wypij, David; Bellinger, David C.; Visconti, Karen J.; du Plessis, Adré J.; Kussman, Barry D.; Scoppettuolo, Lisa A.; Pigula, Frank; Jonas, Richard A.; Newburger, Jane W.

2009-01-01

Objective Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing two-ventricle repair in infancy and to determine risk factors associated with such injury. Methods Forty-eight infants enrolled in a trial comparing two different hematocrits during surgical repair of congenital heart disease underwent brain MRI scans and neurodevelopmental testing at one year of age. Results Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional MRI sequences. Subjects who had foci of hemosiderin had a significantly lower Psychomotor Developmental Index at one year of age (79.6 ± 16.5, mean ± SD) compared with subjects who did not have these foci (89.5 ± 15.3; p=0.04). Older age at surgery and diagnostic group were significantly associated with presence of hemosiderin foci. Only one subject had a small stroke (2%) and two had periventricular leukomalacia (4%). Conclusions Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in MRI studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis and not risk factors associated with brain injury in previous studies suggests that the etiology and pathogenesis of this abnormality is different from ischemic brain lesions reported previously. PMID:19619781

Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness.

PubMed

Menegakis, Apostolos; De Colle, Chiara; Yaromina, Ala; Hennenlotter, Joerg; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Noell, Susan; Tatagiba, Marcos; Brucker, Sara; Wallwiener, Diethelm; Boeke, Simon; Ricardi, Umberto; Baumann, Michael; Zips, Daniel

2015-09-01

To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mean frequency and relative fluorescence intensity measurement of γ-H2AX foci dose response in PBL exposed to γ-irradiation: An inter- and intra-laboratory comparison and its relevance for radiation triage.

PubMed

Venkateswarlu, Raavi; Tamizh, Selvan G; Bhavani, Manivannan; Kumar, Arun; Alok, Amit; Karthik, Kanagaraj; Kalra, Namita; Vijayalakshmi, J; Paul, Solomon F D; Chaudhury, N K; Venkatachalam, Perumal

2015-12-01

Measurement of γ-H2AX protein changes in the peripheral blood lymphocytes (PBL) of individuals exposed to ionizing radiation is a simple, sensitive, and rapid assay for radiation triage and early marker of dose estimation. The qualitative and quantitative measurements of the protein changes were examined using flow cytometry and microscopy. Whole blood and isolated lymphocytes were exposed in vitro between 0.1 and 5 Gy doses of (60) Co γ-radiation at a dose rate of 1 Gy/min. Radiation induced γ-H2AX foci frequency (n = 3) and relative fluorescence intensity (n = 7) in PBL was measured at 0.5 and 2 hrs postexposure. The observed dose response for γ-H2AX foci frequency at both time points, for whole blood and isolated lymphocytes did not show any significant (P > 0.05) differences. However, when compared with γ-H2AX foci frequency scored manually (microscopy), the semiautomated analysis (captured images) showed a better correlation (r(2) = 0.918) than that obtained with automated (Metafer) scoring (r(2) = 0.690). It is noteworthy to mention that, the γ-H2AX foci frequency quantified using microscopy showed a dose dependent increase up to 2 Gy and the relative fluorescence intensity (RFI) measured with flow cytometry revealed an increase up to 5 Gy in the PBL exposed in vitro. Moreover, a better correlation was observed between the γ-H2AX foci frequency obtained by manual scoring and RFI (r(2) = 0.910). Kinetic studies showed that the γ-H2AX foci remain more or less unchanged up to 4 hrs and reduces gradually over 48 hrs of postexposure at 37°C. Further, inter and intra-laboratory comparisons showed consistency in the scoring of γ-H2AX foci frequency by manual and semiautomated scoring. The overall results suggest that measurement of γ-H2AX (microscopy and flow cytometry) should be employed within 4 to 6 hrs for a reliable dosimetry either by sharing the work load between the laboratories or investing more manpower; however, triage can be possible even up to 48 hrs of postirradiation. © 2015 International Society for Advancement of Cytometry.

DNA DSB measurements and modelling approaches based on gamma-H2AX foci time evolution

NASA Astrophysics Data System (ADS)

Esposito, Giuseppe; Campa, Alessandro; Antonelli, Francesca; Mariotti, Luca; Belli, Mauro; Giardullo, Paola; Simone, Giustina; Antonella Tabocchini, Maria; Ottolenghi, Andrea

DNA double strand breaks (DSBs) induced by ionising radiation are considered the main dam-age related to the deleterious consequences in the cells. Unrepaired or mis-repaired DSBs can cause mutations or loss of chromosome regions which can eventually lead to cell death or neo-plastic transformation. Quantification of the number and complexity of DSBs induced by low doses of radiation remains a complex problem. About ten years ago Rogakou et al. proposed an immunofluorescent technique able to detect even a single DSB per cell. This approach is based on the serine 139 phosphorylation of many molecules (up to 2000) of histone H2AX (γg-H2AX) following the induction of a DSB in the DNA. DSB can be visualized as foci by immunofluores-cence by using phospho-specific antibodies, so that enumeration of foci can be used to measure DSB induction and processing. It is still not completely clear how γ-H2AX dephosphorylation takes place; however it has been related with DSB repair, in particular with the efficiency of DSB repair. In this work we analyse the H2AX phosphorylation-dephosphorylation kinetics after irradiation of primary human fibroblasts (AG1522 cell line) with radiation of differing quality, that is γ-rays and α-particles (125 keV/µm), with the aim of comparing the time evolution of γ-H2AX foci. Our results show that, after a dose of 0.5 Gy, both γ-rays and α-particles induce the maximum number of γ-H2AX foci within 30 minutes from irradiation, that this number depends on the radiation type and is consistent with the number of track traversal in α-irradiated nuclei, that the dephosphorylation kinetics are very different, being the α-induced foci rate of disappearence slower than that of γ-induced foci. In this work a modellistic approach to estimate the number of DSB induced by γ-rays detectable by using the γ-H2AX assay is presented. The competing processes of appearance and disappearance of visible foci will be modeled taking into account the phosphorylation and dephosphorylation phenomena. The effect of possible overlapping DSB induced at short distance (within 2 Mbp) will be also taken into account. Moreover, for charged particles (in particular for α-particles) the average number of DSB per focus is calculated.

Increased γ-H2A.X Intensity in Response to Chronic Medium-Dose-Rate γ-Ray Irradiation

PubMed Central

Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

2012-01-01

Background The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. Methodology/Principal Findings We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G1 phase, although no significant difference was observed in G2/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G1 phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G1 phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Conclusions Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation. PMID:23028931

[The pathogenic ecology research on plague in Qinghai plateau].

PubMed

Dai, Rui-xia; Wei, Bai-qing; Li, Cun-xiang; Xiong, Hao-ming; Yang, Xiao-yan; Fan, Wei; Qi, Mei-ying; Jin, Juan; Wei, Rong-jie; Feng, Jian-ping; Jin, Xing; Wang, Zu-yun

2013-12-01

To study the pathogenic ecology characteristics of plague in Qinghai plateau. Applied molecular biology techniques, conventional technologies and geographic information system (GIS) to study phenotypic traits, plasmid spectrum, genotype, infected host and media spectrum etc.of 952 Yersinia pestis strains in Qinghai plateau plague foci, which were separated from different host and media in different regions during 1954 to 2012. The ecotypes of these strains were Qingzang plateau (91.49%, 871/952),Qilian mountain (6.41%, 61/952) and Microtus fuscus (1.26%, 12/952).83.6% (796/952) of these strains contained all the 4 virulence factors (Fr1, Pesticin1,Virulence antigen, and Pigmentation), 93.26% (367/392) were velogenic strains confirmed by virulence test.725 Yersinia pestis strains were separated from Qinghai plateau plague foci carried 9 kinds of plasmid, among which 713 strains from Marmot himalayan plague foci carried 9 kinds of plasmid, the Mr were 6×10(6), 7×10(6), 23×10(6), 27×10(6), 30×10(6), 45×10(6), 52×10(6), 65×10(6) and 92×10(6) respectively. 12 Yersinia pestis strains were separated from Microtus fuscus plague foci carried only 3 kinds of plasmid, the Mr were 6×10(6), 45×10(6), 65×10(6). Meanwhile, the strains carrying large plasmid (52×10(6), 65×10(6) and 92×10(6)) were only distributed in particular geographical location, which had the category property. The research also confirmed that 841 Yersinia pestis strains from two kinds of plague foci in Qinghai plateau had 11 genomovars. The strains of Marmot himalayan plague foci were given priority to genomovar 5 and 8, amounted to 611 strains, genomovar 8 accounted for 56.00% (471/841), genomovar 5 accounted for 23.07% (194/841). Besides, 3 new genomovars, including new 1(62 strains), new 2(52 strains), new 3(48 strains) were newly founded, and 12 strains of Microtus fuscus plague foci were genomovar 14. The main host and media of Qinghai plateau plague foci directly affected the spatial distribution regularities of plague epidemic and the pathogens characteristics, meanwhile the polymorphism of plague ecological geographic landscape leds to the complexity of Yersinia pestis' genotype.

Melorheostosis with bilateral involvement in a black African patient.

PubMed

Biaou, Olivier; Avimadje, Martin; Guira, Oumar; Adjagba, Alex; Zannou, Marcel; Hauzeur, Jean-Philippe

2004-01-01

Melorheostosis is a rare chronic bone disease of unknown etiology that often affects a single limb. Onset usually occurs in childhood or early adolescence. A flowing wax appearance along the surface of the bone and multiple areas of bone sclerosis produce a typical radiographic picture. We describe the first case reported in a black African, in whom an exceedingly rare feature was a bilateral distribution of the lesions.

Sarcoidosis: nail dystrophy without underlying bone changes.

PubMed

Wakelin, S H; James, M P

1995-06-01

Sarcoidosis is a chronic granulomatous disease of unknown origin that affects multiple organs and may present with a variety of skin lesions. Involvement of the nails is rare and almost invariably associated with underlying bone disease. We describe a patient with sarcoid nail dystrophy in whom this diagnosis was confirmed by a proximal nail fold biopsy. Radiologic investigation did not show evidence of an associated bone dystrophy in this case.

Separate channels for processing form, texture, and color: evidence from FMRI adaptation and visual object agnosia.

PubMed

Cavina-Pratesi, C; Kentridge, R W; Heywood, C A; Milner, A D

2010-10-01

Previous neuroimaging research suggests that although object shape is analyzed in the lateral occipital cortex, surface properties of objects, such as color and texture, are dealt with in more medial areas, close to the collateral sulcus (CoS). The present study sought to determine whether there is a single medial region concerned with surface properties in general or whether instead there are multiple foci independently extracting different surface properties. We used stimuli varying in their shape, texture, or color, and tested healthy participants and 2 object-agnosic patients, in both a discrimination task and a functional MR adaptation paradigm. We found a double dissociation between medial and lateral occipitotemporal cortices in processing surface (texture or color) versus geometric (shape) properties, respectively. In Experiment 2, we found that the medial occipitotemporal cortex houses separate foci for color (within anterior CoS and lingual gyrus) and texture (caudally within posterior CoS). In addition, we found that areas selective for shape, texture, and color individually were quite distinct from those that respond to all of these features together (shape and texture and color). These latter areas appear to correspond to those associated with the perception of complex stimuli such as faces and places.

Non-descanned multifocal multiphoton microscopy with a multianode photomultiplier tube

PubMed Central

Cha, Jae Won; Yew, Elijah Y. S.; Kim, Daekeun; Subramanian, Jaichandar; Nedivi, Elly; So, Peter T. C.

2015-01-01

Multifocal multiphoton microscopy (MMM) improves imaging speed over a point scanning approach by parallelizing the excitation process. Early versions of MMM relied on imaging detectors to record emission signals from multiple foci simultaneously. For many turbid biological specimens, the scattering of emission photons results in blurred images and degrades the signal-to-noise ratio (SNR). We have recently demonstrated that a multianode photomultiplier tube (MAPMT) placed in a descanned configuration can effectively collect scattered emission photons from each focus into their corresponding anodes significantly improving image SNR for highly scattering specimens. Unfortunately, a descanned MMM has a longer detection path resulting in substantial emission photon loss. Optical design constraints in a descanned geometry further results in significant optical aberrations especially for large field-of-view (FOV), high NA objectives. Here, we introduce a non-descanned MMM based on MAPMT that substantially overcomes most of these drawbacks. We show that we improve signal efficiency up to fourfold with limited image SNR degradation due to scattered emission photons. The excitation foci can also be spaced wider to cover the full FOV of the objective with minimal aberrations. The performance of this system is demonstrated by imaging interneuron morphological structures deep in the brains of living mice. PMID:25874160

Multiple foci of spatial attention in multimodal working memory.

PubMed

Katus, Tobias; Eimer, Martin

2016-11-15

The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions. Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA/CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In the same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile/visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. Our results reveal distinct foci of tactile and visual spatial attention that were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are activated through modality-specific processes that can operate simultaneously and largely independently of each other. Copyright © 2016 Elsevier Inc. All rights reserved.

Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition

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

Matsumoto, Hotaru; Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp; Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto

2016-07-29

We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of themore » SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. -- Highlights: •Puromycin exhibits the O-propargyl-puromycin effect. •Puromycin induces SUMO redistribution upon proteasome inhibition. •Ubiquitin and RNF4 accumulate at PML-nuclear bodies with SUMO-2/3. •The ubiquitin family may function in nuclear sequestration of immature proteins.« less

Radioisotope bone scanning in a case of sarcoidosis

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

Cinti, D.C.; Hawkins, H.B.; Slavin, J.D. Jr.

1985-03-01

The application of radioisotope scanning to osseous involvement from systemic sarcoidosis has been infrequently described in the scientific literature. Most commonly, the small bones of the hands and feet are affected if sarcoidosis involves the skeleton. Nonetheless, there are also occasional manifestations of sarcoid in the skull, long bones, and vertebral bodies. This paper describes a case of sarcoid involving the lung parenchyma with multiple lesions in the skull and ribs demonstrated by bone scanning with Tc-99m MDP. Following treatment with steroids, the bone scan showed complete resolution of the rib lesions and almost complete resolution of the lesions inmore » the calvarium.« less

Purinergic signalling in bone

PubMed Central

Rumney, Robin M. H.; Wang, Ning; Agrawal, Ankita; Gartland, Alison

2012-01-01

Purinergic signaling in bone was first proposed in the early 1990s with the observation that extracellular ATP could modulate events crucial to the normal functioning of bone cells. Since then the expression of nearly all the P2Y and P2X receptors by osteoblasts and osteoclasts has been reported, mediating multiple processes including cell proliferation, differentiation, function, and death. This review will highlight the most recent developments in the field of purinergic signaling in bone, with a special emphasis on recent work resulting from the European Framework 7 funded collaboration ATPBone, as well as Arthritis Research UK and Bone Research Society supported projects. PMID:23049524

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

PubMed

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

2017-05-01

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

Separate Primary Melanomas of the Bulbar Conjunctiva and Eyelid Skin: Clinical Implications of Multiple Primary Melanomas.

PubMed

Jacinto, Frances A; Fisher, George H; Espana, Edgar M; Leyngold, Ilya M; Margo, Curtis E

2016-10-01

We report a patient with previous in situ melanoma of the forehead skin who was referred for treatment of a bulbar conjunctival melanoma and a separate superficially invasive melanoma of the eyelid skin, and we offer a review of the biological and clinical implications of patients who have multiple primary melanomas. This article offers a clinicopathological correlation with a review of the relevant literature. An 80-year-old white man was referred for evaluation of a suspicious conjunctival tumor and a lower-eyelid lesion. Excisional biopsies revealed that both were primary melanomas arising within in situ disease. Over the span of 25 years, the patient had three separate foci of in situ melanoma, two of which spawned invasive melanoma. Separate melanomas arising from the bulbar conjunctiva and eyelid skin have rarely been reported. Multiple primary melanomas of the skin, however, are not uncommon. Based on studies of persons with multiple cutaneous melanomas, the prognosis is best predicted by the tumor with the greatest depth of invasion. Patients with multiple melanomas should be examined for dysplastic nevi, additional cutaneous melanomas, and screened periodically for future lesions. Ongoing studies enrolling patients with multiple primary melanomas are attempting to generate insights into low-penetrance susceptibility genes.

Sudden multiple fractures in a patient with sarcoidosis in multiple organs.

PubMed

Sada, Mitsuru; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

2014-04-07

A 30-year-old man who incidentally fractured his right olecranon and other multiple phalanges was admitted to our hospital. He had a 2-year history of uveitis and bilateral hilar lymphadenopathy (BHL), and pulmonary sarcoidosis was diagnosed from transbronchial lung biopsy. Right elbow arthrodesis was performed, and biopsied specimens showed non-caseating epithelioid cell granuloma, suggesting osseous sarcoidosis. He was discharged uneventfully without further treatment, but BHL had progressed with the appearance of lung parenchymal lesions 3 months later. At that time, involvement of other organs was also noted on Gallium-67 scintigraphy, showing accumulations in BHL, axillary and inguinal lymph nodes, enlarged liver and spleen and subcutaneous areas. After initiation of steroid therapy, multiple organ involvement improved, and no further bone involvement has been recognised to date. Osseous sarcoidosis complicated by bone fracture is an extremely rare presentation, but should be considered in patients with sarcoidosis, especially when multiple organs are involved.

From Connectivity Models to Region Labels: Identifying Foci of a Neurological Disorder

PubMed Central

Venkataraman, Archana; Kubicki, Marek; Golland, Polina

2014-01-01

We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. We employ the variational expectation-maximization algorithm to fit the model and subsequently identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia. PMID:23864168

FOCIS: A forest classification and inventory system using LANDSAT and digital terrain data

NASA Technical Reports Server (NTRS)

Strahler, A. H.; Franklin, J.; Woodcook, C. E.; Logan, T. L.

1981-01-01

Accurate, cost-effective stratification of forest vegetation and timber inventory is the primary goal of a Forest Classification and Inventory System (FOCIS). Conventional timber stratification using photointerpretation can be time-consuming, costly, and inconsistent from analyst to analyst. FOCIS was designed to overcome these problems by using machine processing techniques to extract and process tonal, textural, and terrain information from registered LANDSAT multispectral and digital terrain data. Comparison of samples from timber strata identified by conventional procedures showed that both have about the same potential to reduce the variance of timber volume estimates over simple random sampling.

A spherical harmonics intensity model for 3D segmentation and 3D shape analysis of heterochromatin foci.

PubMed

Eck, Simon; Wörz, Stefan; Müller-Ott, Katharina; Hahn, Matthias; Biesdorf, Andreas; Schotta, Gunnar; Rippe, Karsten; Rohr, Karl

2016-08-01

The genome is partitioned into regions of euchromatin and heterochromatin. The organization of heterochromatin is important for the regulation of cellular processes such as chromosome segregation and gene silencing, and their misregulation is linked to cancer and other diseases. We present a model-based approach for automatic 3D segmentation and 3D shape analysis of heterochromatin foci from 3D confocal light microscopy images. Our approach employs a novel 3D intensity model based on spherical harmonics, which analytically describes the shape and intensities of the foci. The model parameters are determined by fitting the model to the image intensities using least-squares minimization. To characterize the 3D shape of the foci, we exploit the computed spherical harmonics coefficients and determine a shape descriptor. We applied our approach to 3D synthetic image data as well as real 3D static and real 3D time-lapse microscopy images, and compared the performance with that of previous approaches. It turned out that our approach yields accurate 3D segmentation results and performs better than previous approaches. We also show that our approach can be used for quantifying 3D shape differences of heterochromatin foci. Copyright © 2016 Elsevier B.V. All rights reserved.

Mlh2 Is an Accessory Factor for DNA Mismatch Repair in Saccharomyces cerevisiae

PubMed Central

Srivatsan, Anjana; Bowen, Nikki; Gries, Kerstin; Desai, Arshad; Putnam, Christopher D.; Kolodner, Richard D.

2014-01-01

In Saccharomyces cerevisiae, the essential mismatch repair (MMR) endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1. PMID:24811092

Atypical progression of multiple myeloma with extensive extramedullary disease.

PubMed Central

Jowitt, S N; Jacobs, A; Batman, P A; Sapherson, D A

1994-01-01

Multiple myeloma is a neoplastic disorder caused by the proliferation of a transformed B lymphoid progenitor cell that gives rise to a clone of immunoglobulin-secreting cells. Other plasma cell tumours include solitary plasmacytoma of bone (SPB) and extramedullary plasmacytomas (EMP). Despite an apparent common origin there exist pathological and clinical differences between these neoplasms and the association between them is not completely understood. A case of IgG multiple myeloma that presented with typical clinical and laboratory features, including a bone marrow infiltrated by well differentiated plasma cells, is reported. The tumour had an unusual evolution, with the development of extensive extramedullary disease while maintaining mature histological features. Images PMID:8163701

Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma.

PubMed

Teoh, G; Anderson, K C

1997-02-01

Adhesion molecules play an important role in the growth regulation and migration of multiple myeloma (MM) cells. They mediate homing of MM cells to the bone marrow and MM cell to bone marrow stromal cell adhesion, with resultant interleukin-6 related autocrine and paracine growth and antiapoptotic affects. Their pattern of expression on tumor cells correlates with the development of plasma cell leukemia or extramedullary disease. Clinically, expression of adhesion molecules on tumor cells or in the serum has already shown prognostic utility. Finally, since adhesion molecules are involved at multiple steps in the pathogenesis of MM, therapeutic studies may target these molecules.

Otogenic pneumocephalus as a complication of multiple myeloma.

PubMed

Maguire, Melissa J; Nath, Uma; Bignardi, Guiseppe E

2012-09-01

We report a case of otogenic pneumocephalus in an 80-year-old woman with multiple myeloma. The pneumocephalus was associated with Haemophilus influenzae otitis media and reactive meningitis in the absence of an intracranial brain abscess. Myeloma causes thinning of bone trabeculae and destructive lytic bone lesions. This can predispose to a risk of pathologic fractures and, in patients with skull vault involvement, to the rare complication of pneumocephalus. Therefore, pneumocephalus should be considered in the differential diagnosis of acute headache in patients with multiple myeloma, especially those with skull vault involvement. Prompt computed tomography and liaison between the otolaryngology and neurology teams may assist in making an early diagnosis and preventing life-threatening intracranial complications.

The use of XFEM to assess the influence of intra-cortical porosity on crack propagation.

PubMed

Rodriguez-Florez, Naiara; Carriero, Alessandra; Shefelbine, Sandra J

2017-03-01

This study aimed at using eXtended finite element method (XFEM) to characterize crack growth through bone's intra-cortical pores. Two techniques were compared using Abaqus: (1) void material properties were assigned to pores; (2) multiple enrichment regions with independent crack-growth possibilities were employed. Both were applied to 2D models of transverse images of mouse bone with differing porous structures. Results revealed that assigning multiple enrichment regions allows for multiple cracks to be initiated progressively, which cannot be captured when the voids are filled. Therefore, filling pores with one enrichment region in the model will not create realistic fracture patterns in Abaqus-XFEM.

Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations.

PubMed

Gupta, Mayetri; Cheung, Ching-Lung; Hsu, Yi-Hsiang; Demissie, Serkalem; Cupples, L Adrienne; Kiel, Douglas P; Karasik, David

2011-06-01

Genome-wide association studies (GWAS) using high-density genotyping platforms offer an unbiased strategy to identify new candidate genes for osteoporosis. It is imperative to be able to clearly distinguish signal from noise by focusing on the best phenotype in a genetic study. We performed GWAS of multiple phenotypes associated with fractures [bone mineral density (BMD), bone quantitative ultrasound (QUS), bone geometry, and muscle mass] with approximately 433,000 single-nucleotide polymorphisms (SNPs) and created a database of resulting associations. We performed analysis of GWAS data from 23 phenotypes by a novel modification of a block clustering algorithm followed by gene-set enrichment analysis. A data matrix of standardized regression coefficients was partitioned along both axes--SNPs and phenotypes. Each partition represents a distinct cluster of SNPs that have similar effects over a particular set of phenotypes. Application of this method to our data shows several SNP-phenotype connections. We found a strong cluster of association coefficients of high magnitude for 10 traits (BMD at several skeletal sites, ultrasound measures, cross-sectional bone area, and section modulus of femoral neck and shaft). These clustered traits were highly genetically correlated. Gene-set enrichment analyses indicated the augmentation of genes that cluster with the 10 osteoporosis-related traits in pathways such as aldosterone signaling in epithelial cells, role of osteoblasts, osteoclasts, and chondrocytes in rheumatoid arthritis, and Parkinson signaling. In addition to several known candidate genes, we also identified PRKCH and SCNN1B as potential candidate genes for multiple bone traits. In conclusion, our mining of GWAS results revealed the similarity of association results between bone strength phenotypes that may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in identifying novel genes and pathways that underlie several correlated phenotypes, as well as in deciphering genetic and phenotypic modularity underlying osteoporosis risk. Copyright © 2011 American Society for Bone and Mineral Research.

Non-invasive photo acoustic approach for human bone diagnosis.

PubMed

Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

2016-12-01

The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via IR sensors, and acoustic wave signals may be detected via sensitive pressure transducer, which is reserved for future realization.

Brief communication: unusual finding at Pueblo Bonito: multiple cases of hyperostosis frontalis interna.

PubMed

Mulhern, Dawn M; Wilczak, Cynthia A; Dudar, J Christopher

2006-08-01

Hyperostosis frontalis interna (HFI) is a disease characterized by excess bone growth on the internal lamina of the frontal bone and, occasionally, other cranial bones. Although the disease is fairly common in modern populations, its etiology is poorly understood. Hyperostosis frontalis interna has been identified in antiquity, primarily in the Old World, but with a much lower frequency than in modern groups. The purpose of the present study is to report multiple cases of HFI at Pueblo Bonito (Chaco Canyon, New Mexico). Twelve out of 37 adults with observable frontal bones exhibited HFI, ranging from mild to severe, including 11 females and one male. This is the first published case report of HFI in archaeological remains from the New World having a frequency comparable with modern groups. Most archaeological cases of HFI are isolated, so comparative data for multiple cases at one site are rare. The results of this study emphasize the importance of looking for HFI in archaeological remains, although it is rarely observed. Possible genetic and environmental factors for the high frequency of HFI at Chaco Canyon are considered, but additional research is needed to discover the etiology and to better understand why HFI sometimes occurs at modern frequencies in ancient populations.

Obesity is a concern for bone health with aging.

PubMed

Shapses, Sue A; Pop, L Claudia; Wang, Yang

2017-03-01

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population. Copyright © 2017 Elsevier Inc. All rights reserved.

Obesity is a concern for bone health with aging

PubMed Central

Shapses, Sue A.; Pop, L. Claudia; Wang, Yang

2017-01-01

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population. PMID:28385284

Idiopathic bone cavities of the mandible: an update on recurrence rates and case report.

PubMed

Horne, Robert P; Meara, Daniel J; Granite, Edwin L

2014-02-01

Idiopathic bone cavities (IBCs) are usually an incidental finding, often found in long bones but also in the craniofacial skeleton. Typically solitary, IBCs can present at multiple sites. Surgical exploration alone has proved effective, although recurrence does occur, particularly in cases with multiple lesions. The average time necessary to observe either recurrence or complete healing has been reported to be more than 3 years. Previously reported low recurrence rates for IBCs in the craniofacial skeleton may have been artificially low because of insufficient long-term follow-up. Providers should be prepared for long-term follow-up and care of these patients. The case of the patient presented here supports the need for long-term follow-up. Copyright © 2014 Elsevier Inc. All rights reserved.

Total Hip Arthroplasty Using a Polished Tapered Cemented Stem in Hereditary Multiple Exostosis

PubMed Central

Kanda, Akio; Kaneko, Kazuo; Obayashi, Osamu; Mogami, Atsuhiko

2016-01-01

A 61-year-old Japanese man underwent right total hip arthroplasty for hereditary multiple exostosis. At first presentation, he had suffered from coxalgia for a long time. On radiographic images, there was a gigantic femoral head, increased shaft angle, and large diameter of the femoral neck. He had also developed coxarthrosis and severe pain of the hip joint. The transformation of the proximal femur bone causes difficulty in setting a cementless total hip prosthesis. Therefore, total hip arthroplasty using a cemented polished tapered stem was performed via a direct lateral approach. Using a cemented polished tapered stem allowed us to deal with the femoral bone transformation and bone substance defectiveness due to exostosis and also minimized the invasiveness of the operation. PMID:27127668

Coralline hydroxyapatite: a bone graft alternative in foot and ankle surgery.

PubMed

Rahimi, F; Maurer, B T; Enzweiler, M G

1997-01-01

The use of coralline hydroxyapatite has become a viable bone grafting alternative. Its efficacy has been well established through multiple human and animal studies. Coralline hydroxyapatite enhances osteogenesis by providing a biocompatible lattice for the passage and assembly of vascular, fibroblastic, and osteoblastic tissues. It also provides support for surrounding osseous structures. The uses of this material are expanding into the realm of foot and ankle surgery. Its consideration as an appropriate bone graft substitute as well as multiple case studies demonstrating its surgical applicability are discussed. The implants utilized at Thorek Hospital and Medical Center over the past eight years, with an average follow-up of three and one-half years, have proven to be a valuable resource for augmentation where an osseous defect has occurred.

Bone Lengthening in the Pediatric Upper Extremity.

PubMed

Farr, Sebastian; Mindler, Gabriel; Ganger, Rudolf; Girsch, Werner

2016-09-07

➤Bone lengthening has been used successfully for several congenital and acquired conditions in the pediatric clavicle, humerus, radius, ulna, and phalanges.➤Common indications for bone lengthening include achondroplasia, radial longitudinal deficiency, multiple hereditary exostosis, brachymetacarpia, symbrachydactyly, and posttraumatic and postinfectious growth arrest.➤Most authors prefer distraction rates of <1 mm/day for each bone in the upper extremity except the humerus, which can safely be lengthened by 1 mm/day.➤Most authors define success by the amount of radiographic bone lengthening, joint motion after lengthening, and subjective patient satisfaction rather than validated patient-related outcome measures.➤Bone lengthening of the upper extremity is associated with a high complication rate, with complications including pin-track infections, fixation device failure, nerve lesions, nonunion, fracture of regenerate bone, and joint dislocations. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Cost of skeletal complications from bone metastases in six European countries.

PubMed

Pereira, J; Body, J-J; Gunther, O; Sleeboom, H; Hechmati, G; Maniadakis, N; Terpos, E; Acklin, Y P; Finek, J; von Moos, R

2016-06-01

Objective Patients with bone metastases or lesions secondary to solid tumors or multiple myeloma often experience bone complications (skeletal-related events [SREs]-radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression); however, recent data that can be used to assess the value of treatments to prevent SREs across European countries are limited. This study aimed to provide estimates of health resource utilization (HRU) and cost associated with all SRE types in Europe. HRU data were reported previously; cost data are reported herein. Methods Eligible patients from 49 centers across Austria (n = 57), the Czech Republic (n = 59), Finland (n = 60), Greece (n = 59), Portugal (n = 59), and Sweden (n = 62) had bone metastases or lesions secondary to breast, lung, or prostate cancer, or multiple myeloma, and ≥1 index SRE (a SRE preceded by a SRE-free period of ≥ 6.5 months). SRE-related costs were estimated from a payer perspective using health resource utilization data from patient charts (before and after the index SRE diagnosis). Country-specific unit costs were from 2010 and local currencies were converted to 2010 euros. Results The mean costs across countries were €7043, €5242, €11,101, and €11,509 per radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression event, respectively. Purchasing power parity (PPP)-adjusted mean cost ratios were similar in most countries, with the exception of radiation to bone. Limitations The overall burden of SREs may have been under-estimated owing to home visits and evaluations outside the hospital setting not being reported here. Conclusions All SREs were associated with substantial costs. Variation in SRE-associated costs between countries was most likely driven by differences in treatment practices and unit costs.

Risk factors for low bone mineral density in children and adolescents with inflammatory bowel disease.

PubMed

Lopes, Letícia Helena Caldas; Sdepanian, Vera Lucia; Szejnfeld, Vera Lúcia; de Morais, Mauro Batista; Fagundes-Neto, Ulysses

2008-10-01

To evaluate bone mineral density of the lumbar spine in children and adolescents with inflammatory bowel disease, and to identify the clinical risk factors associated with low bone mineral density. Bone mineral density of the lumbar spine was evaluated using dual-energy X-ray absorptiometry (DXA) in 40 patients with inflammatory bowel disease. Patients were 11.8 (SD = 4.1) years old and most of them were male (52.5%). Multiple linear regression analysis was performed to identify potential associations between bone mineral density Z-score and age, height-for-age Z-score, BMI Z-score, cumulative corticosteroid dose in milligrams and in milligrams per kilogram, disease duration, number of relapses, and calcium intake according to the dietary reference intake. Low bone mineral density (Z-score bellow -2) was observed in 25% of patients. Patients with Crohn's disease and ulcerative colitis had equivalent prevalence of low bone mineral density. Multiple linear regression models demonstrated that height-for-age Z-score, BMI Z-score, and cumulative corticosteroid dose in mg had independent effects on BMD, respectively, beta = 0.492 (P = 0.000), beta = 0.460 (P = 0.001), beta = - 0.014 (P = 0.000), and these effects remained significant after adjustments for disease duration, respectively, beta = 0.489 (P = 0.013), beta = 0.467 (P = 0.001), and beta = - 0.005 (P = 0.015). The model accounted for 54.6% of the variability of the BMD Z-score (adjusted R2 = 0.546). The prevalence of low bone mineral density in children and adolescents with inflammatory bowel disease is considerably high and independent risk factors associated with bone mineral density are corticosteroid cumulative dose in milligrams, height-for-age Z-score, and BMI Z-score.

Combined process automation for large-scale EEG analysis.

PubMed

Sfondouris, John L; Quebedeaux, Tabitha M; Holdgraf, Chris; Musto, Alberto E

2012-01-01

Epileptogenesis is a dynamic process producing increased seizure susceptibility. Electroencephalography (EEG) data provides information critical in understanding the evolution of epileptiform changes throughout epileptic foci. We designed an algorithm to facilitate efficient large-scale EEG analysis via linked automation of multiple data processing steps. Using EEG recordings obtained from electrical stimulation studies, the following steps of EEG analysis were automated: (1) alignment and isolation of pre- and post-stimulation intervals, (2) generation of user-defined band frequency waveforms, (3) spike-sorting, (4) quantification of spike and burst data and (5) power spectral density analysis. This algorithm allows for quicker, more efficient EEG analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Opposed hemispheric specializations for human hypersexuality and orgasm?

PubMed

Suffren, Sabrina; Braun, Claude M J; Guimond, Anik; Devinsky, Orrin

2011-05-01

With a multiple case report analysis we demonstrate that hypersexuality more often results from right hemisphere (RH) (n=26) than left hemisphere (LH) (n=7) lesions, possibly because of LH release after the RH lesion, and that ictal orgasm more often occurs in patients with right-sided (n=23) than left-sided (n=8) seizure foci, with the symptom probably resulting from RH activation. The LH may be specialized for increasing sexual tension, whereas the RH may be specialized for release of this tension (orgasm), the former being catabolic and the latter anabolic. Several other interpretations of the findings are also discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Lactococcus lactis subsp. lactis infection in Bester sturgeon, a cultured hybrid of Huso huso × Acipenser ruthenus, in Taiwan.

PubMed

Chen, Ming-Hui; Hung, Shao-Wen; Shyu, Ching-Lin; Lin, Cheng-Chung; Liu, Pan-Chen; Chang, Chen-Hsuan; Shia, Wei-Yau; Cheng, Ching-Fu; Lin, Shiun-Long; Tu, Ching-Yu; Lin, Yu-Hsing; Wang, Way-Shyan

2012-10-01

Approximately 5300 hybrid sturgeons with an average body weight of 600-800 g were farmed in 3 round tankers measuring 3m in diameter each containing 28,000 L of aerated groundwater. According to the owner's description, the diseased fish had anorexia, pale body color, and reddish spots on the abdomen. The morbidity and lethality rates in this outbreak were about 70% (3706/5300) and 100% (3706/3706), respectively. The clinical examination revealed enteritis, enlarged abdomen, and rapid respiration rate. The gross findings revealed a volume of about 4 mL of ascites. The histopathological examination showed multiple massive, hemorrhagic or coagulative necrotic foci in the liver and spleen. Furthermore, there was diffuse infiltration of glycogen in hepatic cells, and a few polymorphonuclear and mononuclear leucocytes were observed surrounding the spleen. Some bacterial clumps were noted around the necrotic foci. We also observed that there was moderate to severe, acute, multifocal, coagulative necrosis in the renal parenchyma, with some necrotic foci present beneath the margin of the kidney. Additionally, multifocal, coagulative necrosis was found in the pancreas. Results of microbiologic examinations, including biochemical characteristics, PCR amplification of 16S rRNA gene, sequencing and comparison, and phylogenetic analysis, revealed the pathogen of this infection was Lactococcus lactis subsp. lactis, and based on the results of an antimicrobial agent sensitivity test the bacterium was only sensitive to ampicillin and florfenicol. Additionally, results of in vivo experimental infections in hybrid tilapia showed that 1×10(8) and 1×10(9) CFU/mL of our isolate caused death in all fish and LD(50) values ranged from 10(2) to 10(5) CFU/mL. To the best of the authors' knowledge, this is the first reported case of Lactococcus lactis subsp. lactis infection in hybrid sturgeon. Copyright © 2011 Elsevier Ltd. All rights reserved.

Factors predictive of immediate breast reconstruction following mastectomy for invasive breast cancer in Australia.

PubMed

Roder, D; Zorbas, H; Kollias, J; Pyke, C; Walters, D; Campbell, I; Taylor, C; Webster, F

2013-12-01

To investigate person, cancer and treatment determinants of immediate breast reconstruction (IBR) in Australia. Bi-variable and multi-variable analyses of the Quality Audit database. Of 12,707 invasive cancers treated by mastectomy circa 1998-2010, 8% had IBR. This proportion increased over time and reduced from 29% in women below 30 years to approximately 1% in those aged 70 years or more. Multiple regression indicated that other IBR predictors included: high socio-economic status; private health insurance; being asymptomatic; a metropolitan rather than inner regional treatment centre; higher surgeon case load; small tumour size; negative nodal status, positive progesterone receptor status; more cancer foci; multiple affected breast quadrants; synchronous bilateral cancer; not having neo-adjuvant chemotherapy, adjuvant radiotherapy or adjuvant hormone therapy; and receiving ovarian ablation. Variations in access to specialty services and other possible causes of variations in IBR rates need further investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unilateral giant cell lesion of the jaw in Noonan syndrome.

PubMed

Eyselbergs, M; Vanhoenacker, F; Hintjens, J; Dom, M; Devriendt, K; Van Dijck, H

2014-01-01

Noonan syndrome (NS) is an etiologically heterogeneous disorder caused by mutations in the RAS-MAPK signaling pathway. Noonan-Like/Multiple Giant Cell Lesion (NL/MGCL) syndrome is initially described as the occurrence of multiple gnathic giant cell lesions in patients with phenotypic features of NS. Nowadays, NS/MGCL syndrome is considered a variant of the NS spectrum rather than a distinct entity. We report the case of a 14-year-old female patient carrying a SOS1 mutation with a unilateral giant cell lesion of the right mandible. Cross-sectional imaging such as CT and MRI are not specific for the diagnosis of oral giant cell lesions. Nonetheless, intralesional scattered foci of low SI on T2-WI, corresponding to hemosiderin deposits due to hemorrhage, can help the radiologist in narrowing down the differential diagnosis of gnathic lesions in patients with NS.

Sarcocystis neurona encephalitis in a dog.

PubMed

Cooley, A J; Barr, B; Rejmanek, D

2007-11-01

A 1.5-year-old male Feist dog was presented to a veterinarian for reluctance to stand on the hind legs. Treatment included dexamethasone and resulted in a favorable initial response, but posterior paresis returned and progressed to recumbency, hyperesthesia, and attempts to bite the owner. The dog was euthanized. The brain was negative for rabies by fluorescent antibody analysis. Multiple foci of encephalitis were found in the cerebrum and particularly in the cerebellum. Protozoa morphologically consistent with Sarcocystis sp. were identified at sites of intense inflammation and malacia. Additionally, multiple schizonts were identified in areas without inflammation. Immunohistochemistry using both polyclonal and monoclonal antibodies specific for Sarcocystis neurona was strongly positive. No reaction to polyclonal antisera for Toxoplasma gondii or Neospora caninum was found. Polymerase chain reaction confirmed that the protozoa were S. neurona. Additional aberrant hosts for S. neurona other than horses have been identified, but S. neurona encephalitis has not been documented previously in the dog.

Adipose, Bone, and Myeloma: Contributions from the Microenvironment.

PubMed

McDonald, Michelle M; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R

2017-05-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide (Podar et al. in Expert Opin Emerg Drugs 14:99-127, 2009). Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90 % of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes, and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.

Increased expression of a set of genes enriched in oxygen binding function discloses a predisposition of breast cancer bone metastases to generate metastasis spread in multiple organs.

PubMed

Capulli, Mattia; Angelucci, Adriano; Driouch, Keltouma; Garcia, Teresa; Clement-Lacroix, Philippe; Martella, Francesco; Ventura, Luca; Bologna, Mauro; Flamini, Stefano; Moreschini, Oreste; Lidereau, Rosette; Ricevuto, Enrico; Muraca, Maurizio; Teti, Anna; Rucci, Nadia

2012-11-01

Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B (HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone. Copyright © 2012 American Society for Bone and Mineral Research.

Simultaneous segmentation of the bone and cartilage surfaces of a knee joint in 3D

NASA Astrophysics Data System (ADS)

Yin, Y.; Zhang, X.; Anderson, D. D.; Brown, T. D.; Hofwegen, C. Van; Sonka, M.

2009-02-01

We present a novel framework for the simultaneous segmentation of multiple interacting surfaces belonging to multiple mutually interacting objects. The method is a non-trivial extension of our previously reported optimal multi-surface segmentation. Considering an example application of knee-cartilage segmentation, the framework consists of the following main steps: 1) Shape model construction: Building a mean shape for each bone of the joint (femur, tibia, patella) from interactively segmented volumetric datasets. Using the resulting mean-shape model - identification of cartilage, non-cartilage, and transition areas on the mean-shape bone model surfaces. 2) Presegmentation: Employment of iterative optimal surface detection method to achieve approximate segmentation of individual bone surfaces. 3) Cross-object surface mapping: Detection of inter-bone equidistant separating sheets to help identify corresponding vertex pairs for all interacting surfaces. 4) Multi-object, multi-surface graph construction and final segmentation: Construction of a single multi-bone, multi-surface graph so that two surfaces (bone and cartilage) with zero and non-zero intervening distances can be detected for each bone of the joint, according to whether or not cartilage can be locally absent or present on the bone. To define inter-object relationships, corresponding vertex pairs identified using the separating sheets were interlinked in the graph. The graph optimization algorithm acted on the entire multiobject, multi-surface graph to yield a globally optimal solution. The segmentation framework was tested on 16 MR-DESS knee-joint datasets from the Osteoarthritis Initiative database. The average signed surface positioning error for the 6 detected surfaces ranged from 0.00 to 0.12 mm. When independently initialized, the signed reproducibility error of bone and cartilage segmentation ranged from 0.00 to 0.26 mm. The results showed that this framework provides robust, accurate, and reproducible segmentation of the knee joint bone and cartilage surfaces of the femur, tibia, and patella. As a general segmentation tool, the developed framework can be applied to a broad range of multi-object segmentation problems.

Osteosclerotic myeloma with polyneuropathy and hypocalcemia.

PubMed

Ludescher, C; Grünewald, K; Fend, F; Dietze, O; Thaler, J; Schmid, K W

1989-04-01

A case is presented of a 46-year-old man with multifocal osteosclerotic bone lesions, peripheral polyneuropathy and hypocalcemia. Histologic examination of a bone marrow biopsy disclosed a multiple myeloma. Immunoelectrophoresis revealed a small M-component identified as IgG-lambda. Osteosclerotic myeloma lacking any osteolytic lesions seems to be very rare and shows several different features as compared with classical myeloma. A review of the current literature suggests that multiple myeloma is not a uniform disease but rather a group of clinical syndromes characterized by the special properties of their proliferating plasma cell clones.

Congenital cutis laxa with ligamentous laxity and delayed development, Dandy-Walker malformation and minor heart and osseous defects.

PubMed

Biver, A; De Rijcke, S; Toppet, V; Ledoux-Corbusier, M; Van Maldergem, L

1994-06-01

We present a female infant exhibiting congenital cutis laxa with retardation of growth and motor development, ligamentous laxity and congenital dislocation of the hips. This connective tissue disorder was associated with Dandy-Walker malformation, atrial and ventricular defect and minor bone abnormalities including multiple wormian bones, abnormal tubulation of long bones and absent twelfth pair of ribs. This association is believed to be unique.

Wideband Single-Crystal Transducer for Bone Characterization

NASA Technical Reports Server (NTRS)

Liang, Yu; Snook, Kevin

2012-01-01

The microgravity conditions of space travel result in unique physiological demands on the human body. In particular, the absence of the continual mechanical stresses on the skeletal system that are present on Earth cause the bones to decalcify. Trabecular structure decreases in thickness and increases in spacing, resulting in decreased bone strength and increased risk of injury. Thus, monitoring bone health is a high priority for long-term space travel. A single probe covering all frequency bands of interest would be ideal for such measurements, and this would also minimize storage space and eliminate the complexity of integrating multiple probes. This invention is an ultrasound transducer for the structural characterization of bone. Such characterization measures features of reflected and transmitted ultrasound signals, and correlates these signals with bone structure metrics such as bone mineral density, trabecular spacing, and thickness, etc. The techniques used to determine these various metrics require measurements over a broad range of ultrasound frequencies, and therefore, complete characterization requires the use of several narrowband transducers. This is a single transducer capable of making these measurements in all the required frequency bands. The device achieves this capability through a unique combination of a broadband piezoelectric material; a design incorporating multiple resonator sizes with distinct, overlapping frequency spectra; and a micromachining process for producing the multiple-resonator pattern with common electrode surfaces between the resonators. This device consists of a pattern of resonator bars with common electrodes that is wrapped around a central mandrel such that the radiating faces of the resonators are coplanar and can be simultaneously applied to the sample to be measured. The device operates as both a source and receiver of acoustic energy. It is operated by connection to an electronic system capable of both providing an excitation signal to the transducer and amplifying the signal received from the transducer. The excitation signal may be either a wide-bandwidth signal to excite the transducer across its entire operational spectrum, or a narrow-bandwidth signal optimized for a particular measurement technique. The transducer face is applied to the skin covering the bone to be characterized, and may be operated in through transmission mode using two transducers, or in pulse-echo mode.

Energy Efficiency of a New Trifocal Intraocular Lens

NASA Astrophysics Data System (ADS)

Vega, F.; Alba-Bueno, F.; Millán, M. S.

2014-01-01

The light distribution among the far, intermediate and near foci of a new trifocal intraocular lens (IOL) is experimentally determined, as a function of the pupil size, from image analysis. The concept of focus energy efficiency is introduced because, in addition to the theoretical diffraction efficiency of the focus, it accounts for other factors that are naturally presented in the human eye such as the level of spherical aberration (SA) upon the IOL, light scattering at the diffractive steps or the depth of focus. The trifocal IOL is tested in-vitro in two eye models: the aberration-free ISO model, and a so called modified-ISO one that uses an artificial cornea with positive spherical SA in instead. The SA upon the IOL is measured with a Hartmann-Shack sensor and compared to the values of theoretical eye models. The results show, for large pupils, a notorious reduction of the energy efficiency of the far and near foci of the trifocal IOL due to two facts: the level of SA upon the IOL is larger than the value the lens is able to compensate for and there is significant light scattering at the diffractive steps. On the other hand, the energy efficiency of the intermediate focus for small pupils is enhanced by the contribution of the extended depth of focus of the near and far foci. Thus, while IOLs manufacturers tend to provide just the theoretical diffraction efficiency of the foci to show which would be the performance of the lens in terms of light distribution among the foci, our results put into evidence that this is better described by using the energy efficiency of the foci.

Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks.

PubMed

Rybak, Paulina; Hoang, Agnieszka; Bujnowicz, Lukasz; Bernas, Tytus; Berniak, Krzysztof; Zarębski, Mirosław; Darzynkiewicz, Zbigniew; Dobrucki, Jerzy

2016-08-02

Phosphorylation of histone H2AX on serine 139 (γH2AX) is an early step in cellular response to a DNA double-strand break (DSB). γH2AX foci are generally regarded as markers of DSBs. A growing body of evidence demonstrates, however, that while induction of DSBs always brings about phosphorylation of histone H2AX, the reverse is not true - the presence of γH2AX foci should not be considered an unequivocal marker of DNA double-strand breaks. We studied DNA damage induced in A549 human lung adenocarcinoma cells by topoisomerase type I and II inhibitors (0.2 μM camptothecin, 10 μM etoposide or 0.2 μM mitoxantrone for 1 h), and using 3D high resolution quantitative confocal microscopy, assessed the number, size and the integrated intensity of immunofluorescence signals of individual γH2AX foci induced by these drugs. Also, investigated was spatial association between γH2AX foci and foci of 53BP1, the protein involved in DSB repair, both in relation to DNA replication sites (factories) as revealed by labeling nascent DNA with EdU. Extensive 3D and correlation data analysis demonstrated that γH2AX foci exhibit a wide range of sizes and levels of H2AX phosphorylation, and correlate differently with 53BP1 and DNA replication. This is the first report showing lack of a link between low level phosphorylation γH2AX sites and double-strand DNA breaks in cells exposed to topoisomerase I or II inhibitors. The data are discussed in terms of mechanisms that may be involved in formation of γH2AX sites of different sizes and intensities.

Explanation for excessive DNA single-strand breaks and endogenous repair foci in pluripotent mouse embryonic stem cells.

PubMed

Banáth, J P; Bañuelos, C A; Klokov, D; MacPhail, S M; Lansdorp, P M; Olive, P L

2009-05-01

Pluripotent mouse embryonic stem cells (mES cells) exhibit approximately 100 large gammaH2AX repair foci in the absence of measurable numbers of DNA double-strand breaks. Many of these cells also show excessive numbers of DNA single-strand breaks (>10,000 per cell) when analyzed using the alkaline comet assay. To understand the reasons for these unexpected observations, various methods for detecting DNA strand breaks were applied to wild-type mES cells and to mES cells lacking H2AX, ATM, or DNA-PKcs. H2AX phosphorylation and expression of other repair complexes were measured using flow and image analysis of antibody-stained cells. Results indicate that high numbers of endogenous gammaH2AX foci and single-strand breaks in pluripotent mES cells do not require ATM or DNA-PK kinase activity and appear to be associated with global chromatin decondensation rather than pre-existing DNA damage. This will limit applications of gammaH2AX foci analysis in mES cells to relatively high levels of initial or residual DNA damage. Excessive numbers of single-strand breaks in the alkaline comet assay can be explained by the vulnerability of replicating chromatin in mES cells to osmotic shock. This suggests that caution is needed in interpreting results with the alkaline comet assay when applied to certain cell types or after treatment with agents that make chromatin vulnerable to osmotic changes. Differentiation of mES cells caused a reduction in histone acetylation, gammaH2AX foci intensity, and DNA single-strand breakage, providing a link between chromatin structural organization, excessive gammaH2AX foci, and sensitivity of replicating mES cell chromatin to osmotic shock.

Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.

PubMed

Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

2016-05-01

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34+Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative high resolution mapping of HvMLH3 foci in barley pachytene nuclei reveals a strong distal bias and weak interference

PubMed Central

Phillips, Dylan; Wnetrzak, Joanna; Nibau, Candida; Barakate, Abdellah; Ramsay, Luke; Wright, Frank; Higgins, James D.; Perry, Ruth M.; Jenkins, Glyn

2013-01-01

In barley (Hordeum vulgare L.), chiasmata (the physical sites of genetic crossovers) are skewed towards the distal ends of chromosomes, effectively consigning a large proportion of genes to recombination coldspots. This has the effect of limiting potential genetic variability, and of reducing the efficiency of map-based cloning and breeding approaches for this crop. Shifting the sites of recombination to more proximal chromosome regions by forward and reverse genetic means may be profitable in terms of realizing the genetic potential of the species, but is predicated upon a better understanding of the mechanisms governing the sites of these events, and upon the ability to recognize real changes in recombination patterns. The barley MutL Homologue (HvMLH3), a marker for class I interfering crossovers, has been isolated and a specific antibody has been raised. Immunolocalization of HvMLH3 along with the synaptonemal complex transverse filament protein ZYP1, used in conjunction with fluorescence in situ hybridization (FISH) tagging of specific barley chromosomes, has enabled access to the physical recombination landscape of the barley cultivars Morex and Bowman. Consistent distal localization of HvMLH3 foci throughout the genome, and similar patterns of HvMLH3 foci within bivalents 2H and 3H have been observed. A difference in total numbers of HvMLH3 foci between these two cultivars has been quantified, which is interpreted as representing genotypic variation in class I crossover frequency. Discrepancies between the frequencies of HvMLH3 foci and crossover frequencies derived from linkage analysis point to the existence of at least two crossover pathways in barley. It is also shown that interference of HvMLH3 foci is relatively weak compared with other plant species. PMID:23554258

Ultraviolet-induced movement of the human DNA repair protein, xeroderma pigmentosum type G, in the nucleus

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

Park, M.S.; Knauf, J.A.; Pendergrass, S.H.

1996-08-06

Xeroderma pigmentosum type G (XPG) is a human genetic disease exhibiting extreme sensitivity to sunlight. XPG patients are defective XPG endonuclease, which is an enzyme essential for DNA repair of the major kinds of solar ultraviolet (UV)-induced DNA damages. Here we describe a novel dynamics of this protein within the cell nucleus after UV irradiation of human cells. USing confocal microscopy, we have localized the immunofluorescent, antigenic signal of XPG protein to foci throughout the cell nucleus. Our biochemical studies also established that XPG protein forms a tight association with nuclear structure(s). In human skin fibroblast cells, the number ofmore » XPG foci decreased within 2 h after UV irradiation, whereas total nuclear XPG fluorescence intensity remained constant, suggesting redistribution of XPG from a limited number of nuclear foci to the nucleus overall. Within 8 h after UV, most XPG antigenic signal was found as foci. Using {beta}-galactosidase-XPG fusion constructs ({beta}-gal-XPG) transfected into HeLa cells, we have identified a single region of XPG that is evidently responsible both for foci formation and for the UV dynamic response. The fusion protein carrying the C terminus of XPG (amino acids 1146-1185) localized {beta}-gal specific antigenic signal to foci and to the nucleolus regions. After UV irradiation, antigenic {beta}-gal translocated reversibly from the subnuclear structures to the whole nucleus with kinetics very similar to the movements of XPG protein. These findings lead us to propose a model in which distribution of XPG protein may regulate the rate of DNA repair within transcriptionally active and inactive compartments of the cell nucleus. 50 refs., 5 figs., 1 tab.« less

Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors

PubMed Central

Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-ping; Young, Lauren F.; Shieh, Jae-Hung; Moore, Malcolm A.; van den Brink, Marcel R.M.; Kusunoki, Yoichiro

2016-01-01

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin−) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. PMID:27169377

FANC Pathway Promotes UV-Induced Stalled Replication Forks Recovery by Acting Both Upstream and Downstream Polη and Rev1

PubMed Central

Renaud, Emilie; Rosselli, Filippo

2013-01-01

To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised DNA polymerases or tolerate the lesions using homologous recombination (HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled replication forks, we analysed the molecular crosstalk between the TLS DNA polymerases Polη and Rev1, the double-strand break repair (DSB)-associated protein MDC1 and the FANC pathway. We describe three novel functional interactions that occur in response to UVC-induced DNA lesions. First, Polη and Rev1, whose optimal expression and/or relocalisation depend on the FANC core complex, act upstream of FANCD2 and are required for the proper relocalisation of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are independently required for optimal BRCA1 relocalisation. While RPA32 phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the basis of the previous observations, we propose that the FANC pathway participates in the rescue of UVC-stalled replication forks in association with TLS by maintaining the integrity of ssDNA regions and by preserving genome stability and preventing the formation of DSBs, the resolution of which would require the intervention of MDC1. PMID:23365640

Increased expression of metalloproteinase-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), and EMMPRIN (CD147) in multiple myeloma.

PubMed

Urbaniak-Kujda, Donata; Kapelko-Slowik, Katarzyna; Prajs, Iwona; Dybko, Jarosław; Wolowiec, Dariusz; Biernat, Monika; Slowik, Miroslaw; Kuliczkowski, Kazimierz

2016-01-01

Activity of metalloproteinases (MMP) is controlled both by specific tissue inhibitors (TIMP) and activators (extracellular matrix metalloproteinase inducer, EMMPRIN). There are few data available concerning concentration the bone marrow of MMP-2, MMP-9, TIMP-1, and TIMP-2, or EMMPRIM expression by bone marrow mesenchymal stromal cells (BMSCs) in patients with multiple myeloma (MM). We studied 40 newly diagnosed, untreated patients: 18 males and 22 females with de novo MM and 11 healthy controls. Bone marrow was collected prior to therapy. BMSCs were derived by culturing bone marrow cells on MesenCult. Protein concentrations were determined in bone marrow plasma and culture supernatants by ELISA. EMMPRIN expression by BMSCs was assessed by flow cytometry. The median concentrations of MMP-9, TIMP-1, and TIMP-2 in both marrow plasma and culture supernatants were significantly higher in MM patients than controls. EMMPRIN expression and ratios MMP-9/TIMP-1 and MMP-2/TIMP-2 were higher in MM patients, our results demonstrate that in MM patients MMP-2 and MMP-9 are secreted in higher amounts and are not balanced by inhibitors.

Towards optical brain imaging: getting light through a bone

NASA Astrophysics Data System (ADS)

Thompson, J. V.; Hokr, B. H.; Nodurft, D. T.; Yakovlev, V. V.

2018-06-01

Optical imaging and detection in biological samples is severely limited by scattering effects. In particular, optical techniques for measuring conditions beneath the skull and within the bone marrow hold significant promise when it comes to speed, sensitivity and specificity. However, the strong optical scattering due to bone hinders the realization of these methods. In this article, we propose a technique to enhance the transmittance of light through bone. This is achieved by injecting light below the top surface of the bone and utilizing multiple scattering to increase transmittance. This technique suggests that enhancements of 2-6 times may be realized by injection of light 1 mm below the surface of the bone. By enhancing the transmittance of light through bone, we will greatly improve our ability to utilize optical methods to better understand and diagnose conditions within biological media.

Chronic myelogenous leukemia in a great horned owl (Bubo virginianus).

PubMed

Wiley, Jennifer L; Whittington, Julia K; Wilmes, Christine M; Messick, Joanne B

2009-03-01

A free-ranging adult female great horned owl (Bubo virginianus) was presented to the Wildlife Medical Clinic at the University of Illinois after being observed with anorexia and decreased activity. A severe leukocytosis (212 400 cells/microl), primarily comprised of mature heterophils, was found at presentation. Results of various diagnostic tests including radiographs, Chlamydophila serologic testing, measurement of Aspergillus antibody and antigen titers, plasma protein electrophoresis, fecal culture and acid-fast staining, coelioscopy, endoscopy, tracheoscopy, exploratory coelomotomy, nuclear scintigraphy, tissue cultures, bone marrow biopsy, and histopathology revealed no underlying cause for the persistent leukocytosis. No response to treatment with antibiotics or antifungal agents was observed, although a transient, significant decrease in the leukocyte count (6200 cells/microl) was observed after treatment with fenbendazole. A presumptive diagnosis of chronic myelogenous leukemia was made based on 3 factors: disease duration of greater than 3 months, a lack of identifiable foci of inflammation, and a lack of response to conventional therapy. The diagnosis was confirmed based on postmortem examination and testing 177 days after initial presentation.

Nonlinear viscoelastic characterization of bovine trabecular bone.

PubMed

Manda, Krishnagoud; Wallace, Robert J; Xie, Shuqiao; Levrero-Florencio, Francesc; Pankaj, Pankaj

2017-02-01

The time-independent elastic properties of trabecular bone have been extensively investigated, and several stiffness-density relations have been proposed. Although it is recognized that trabecular bone exhibits time-dependent mechanical behaviour, a property of viscoelastic materials, the characterization of this behaviour has received limited attention. The objective of the present study was to investigate the time-dependent behaviour of bovine trabecular bone through a series of compressive creep-recovery experiments and to identify its nonlinear constitutive viscoelastic material parameters. Uniaxial compressive creep and recovery experiments at multiple loads were performed on cylindrical bovine trabecular bone samples ([Formula: see text]). Creep response was found to be significant and always comprised of recoverable and irrecoverable strains, even at low stress/strain levels. This response was also found to vary nonlinearly with applied stress. A systematic methodology was developed to separate recoverable (nonlinear viscoelastic) and irrecoverable (permanent) strains from the total experimental strain response. We found that Schapery's nonlinear viscoelastic constitutive model describes the viscoelastic response of the trabecular bone, and parameters associated with this model were estimated from the multiple load creep-recovery (MLCR) experiments. Nonlinear viscoelastic recovery compliance was found to have a decreasing and then increasing trend with increasing stress level, indicating possible stiffening and softening behaviour of trabecular bone due to creep. The obtained parameters from MLCR tests, expressed as second-order polynomial functions of stress, showed a similar trend for all the samples, and also demonstrate stiffening-softening behaviour with increasing stress.

Spinal focal lesion detection in multiple myeloma using multimodal image features

NASA Astrophysics Data System (ADS)

Fränzle, Andrea; Hillengass, Jens; Bendl, Rolf

2015-03-01

Multiple myeloma is a tumor disease in the bone marrow that affects the skeleton systemically, i.e. multiple lesions can occur in different sites in the skeleton. To quantify overall tumor mass for determining degree of disease and for analysis of therapy response, volumetry of all lesions is needed. Since the large amount of lesions in one patient impedes manual segmentation of all lesions, quantification of overall tumor volume is not possible until now. Therefore development of automatic lesion detection and segmentation methods is necessary. Since focal tumors in multiple myeloma show different characteristics in different modalities (changes in bone structure in CT images, hypointensity in T1 weighted MR images and hyperintensity in T2 weighted MR images), multimodal image analysis is necessary for the detection of focal tumors. In this paper a pattern recognition approach is presented that identifies focal lesions in lumbar vertebrae based on features from T1 and T2 weighted MR images. Image voxels within bone are classified using random forests based on plain intensities and intensity value derived features (maximum, minimum, mean, median) in a 5 x 5 neighborhood around a voxel from both T1 and T2 weighted MR images. A test data sample of lesions in 8 lumbar vertebrae from 4 multiple myeloma patients can be classified at an accuracy of 95% (using a leave-one-patient-out test). The approach provides a reasonable delineation of the example lesions. This is an important step towards automatic tumor volume quantification in multiple myeloma.

Carcinoma in gastric hyperplastic polyps: A phenotypic study

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

Zea-Iriarte, W.L.; Sekine, Ichiro; Itsuno, Minoru

1996-02-01

One-hundred twelve hyperplastic polyps were analyzed. The aim was to study their malignant transformation. Among them, four hyperplastic polyps harbored adenocarcinoma; two were from our own institution (1.8%). The majority were pedunculated and located in the antrum with an average of 14.5 mm in diameter. The four polyps bore well-differentiated adenocarcinoma. Dysplasia and intestinal metaplasia were detected in two and three polyps, respectively. The cancer and dysplastic foci shared the same type of neutral and acid mucosubstances. p53 oncoprotein was positive in three cancer foci and in the dysplastic areas, and nucleolar organizer region counts were higher in the cancermore » foci. In conclusion, hyperplastic polyps have malignant potential. Such possibility increases in polyps larger than 14.5 mm. In our cases, the carcinoma foci may have arisen from dysplastic areas. Once the neoplastic changes occur, the cancer cells proliferate and behave as other adenocarcinomas of the stomach. 40 refs., 7 figs., 5 tabs.« less

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

PubMed

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.

Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break

PubMed Central

Brown, M. Scott; Grubb, Jennifer; Zhang, Annie; Rust, Michael J.; Bishop, Douglas K.

2015-01-01

The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks (DSBs). Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci. Here we show these Rad51-Dmc1 co-foci are often arranged in pairs separated by distances of up to 400 nm. Paired co-foci remain prevalent when DSBs are dramatically reduced or when strand exchange or synapsis is blocked. Super-resolution dSTORM microscopy reveals that individual foci observed by conventional light microscopy are often composed of two or more substructures. The data support a model in which the two tracts of ssDNA formed by a single DSB separate from one another by distances of up to 400 nm, with both tracts often bound by one or more short (about 100 nt) Rad51 filaments and also by one or more short Dmc1 filaments. PMID:26719980

Bone density in the obese child - clinical considerations and diagnostic challenges

PubMed Central

Kelley, Jennifer; Crabtree, Nicola; Zemel, Babette S.

2017-01-01

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children. PMID:28105511

Repairing Fractured Bones by Use of Bioabsorbable Composites

NASA Technical Reports Server (NTRS)

Farley, Gary L.

2006-01-01

A proposed method of surgical repair of fractured bones would incorporate recent and future advances in the art of composite materials. The composite materials used in this method would be biocompatible and at least partly bioabsorbable: that is, during the healing process following surgery, they would be wholly or at least partly absorbed into the bones and other tissues in which they were implanted. Relative to the traditional method, the proposed method would involve less surgery, pose less of a risk of infection, provide for better transfer of loads across fracture sites, and thereby promote better healing while reducing the need for immobilization by casts and other external devices. One requirement that both the traditional and proposed methods must satisfy is to fix the multiple segments of a broken bone in the correct relative positions. Mechanical fixing techniques used in the traditional method include the use of plates spanning the fracture site and secured to the bone by screws, serving of wire along the bone across the fracture site, insertion of metallic intramedullary rods through the hollow portion of the fractured bone, and/or inserting transverse rods through the bone, muscle, and skin to stabilize the fractured members. After the bone heals, a second surgical operation is needed to remove the mechanical fixture(s). In the proposed method, there would be no need for a second surgical operation. The proposed method is based partly on the observation that in the fabrication of a structural member, it is generally more efficient and reliable to use multiple small fasteners to transfer load across a joint than to use a single or smaller number of larger fasteners, provided that the stress fields of neighboring small fasteners do not overlap or interact. Also, multiple smaller fasteners are more reliable than are larger and fewer fasteners. However, there is a trade-off between structural efficiency and the cost of insertion time and materials. The proposed method is further based partly on the conjecture that through-the-thickness reinforcements could be excellent for fixing bone segments for surgical repair. The through-the-thickness reinforcements would superficially resemble nails in both form and function. Denoted small-diameter rods (SDRs) to distinguish them from other narrow rods, these reinforcements would be shot or otherwise inserted through adjacent segments of fractured bone to fix them in their correct relative positions (see figure). Shot insertion would be effected by use an applicator that would amount to a miniaturized and highly refined version of the pneumatic guns often used in carpentry to drive nails and brads. The applicator, envisioned to be about the size of a ball-point-pen, would be driven by pressurized carbon dioxide. To further promote stabilization of the segments, layers of bone glue could be applied to the fracture surfaces prior to insertion of the SDRs. The bone glue could be therapeutically loaded with chemicals to promote growth of bone and fight infection

Non Secretory Multiple Myeloma With Extensive Extramedullary Plasmacytoma: A Diagnostic Dilemma

PubMed Central

Low, Soo Fin; Mohd Tap, Nor Hanani; Kew, Thean Yean; Ngiu, Chai Soon; Sridharan, Radhika

2015-01-01

Multiple myeloma (MM) is characterized by progressive proliferation of malignant plasma cells, usually initiating in the bone marrow. MM can affect any organ; a total of 7 - 18% of patients with MM demonstrate extramedullary involvement at diagnosis. Non-secretory multiple myeloma (NSMM) is a rare variant that accounts for 1 - 5% of all cases of multiple myeloma. The disease is characterized by the absence of monoclonal gammopathy in serum and urine electrophoresis. Our case report highlights the diagnostic challenge of a case of NSMM with extensive extramedullary involvement in a young female patient who initially presented with right shoulder pain and bilateral breasts lumps. Skeletal survey showed multiple lytic bony lesions. The initial diagnosis was primary breast carcinoma with osseous metastases. No monoclonal gammopathy was found in the serum or urine electrophoresis. Bone marrow and breast biopsies revealed marked plasmacytosis. The diagnosis was delayed for a month in view of the lack of clinical suspicion of multiple myeloma in a young patient and scant biochemical expression of non-secretory type of multiple myeloma. PMID:26528383

Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis.

PubMed

Dovio, Andrea; Perazzolo, Laura; Osella, Giangiacomo; Ventura, Massimo; Termine, Angela; Milano, Eva; Bertolotto, Antonio; Angeli, Alberto

2004-10-01

Glucocorticoid (GC)-induced osteoporosis is the leading form of secondary osteoporosis. Bone loss can be rapid. However, longitudinal studies at the very beginning of treatment are scarce. Patients relapsing from multiple sclerosis are treated with high-dose, short-term iv GCs. A number of them are young, without concomitant disease affecting bone and with no substantial impairment of mobility. Such patients were selected for the present study. Thirteen patients suffering from multiple sclerosis [11 females, two males; age 32 +/- 2 yr (mean +/- se)] and receiving iv methylprednisolone 15 mg/kg daily for 10 d completed the study. We measured serum osteocalcin (OC), aminoterminal propeptide of type I collagen (PINP), bone isoform of alkaline phosphatase (bALP), carboxyterminal telopeptide of type I collagen (CTX), and urinary calcium/creatinine ratio (uCa/Cr) during the 10-d cycle and 3 months later. Dual-energy x-ray absorptiometry and calcaneal quantitative ultrasonometry were performed before and 6 months after therapy. We found an immediate, impressive fall of OC and PINP (-80 +/- 3 and -54 +/- 5% at d 2, respectively), which persisted throughout the whole treatment period (P < 0.0001 for both markers). bALP levels showed only a modest decrease at d 6 (-19 +/- 7%, P < 0.05), with subsequent return to baseline in d 7-10. After 3 months, OC, PINP, and bALP levels rose to +51 +/- 22, +37 +/- 16 (not significant), and +61 +/- 17% (P < 0.01) with respect to baseline, respectively. uCa/Cr and CTX showed a progressive, marked increase during treatment, peaking at d 7-9 (+92 +/- 44 and +149 +/- 63%, respectively), with subsequent decrement at d 10 (P < 0.01 and P < 0.05, respectively) despite continuing GC administration. After 3 months, uCa/Cr and CTX levels were also higher than baseline. No change in quantitative ultrasonometry parameters and bone mineral density was observed 6 months after therapy. In conclusion, high-dose, short-term iv GC regimens cause an immediate and persistent decrease in bone formation and a rapid and transient increase of bone resorption. Our data also support the concept that discontinuation of such regimens is followed by a high bone turnover phase.

[Cat-scratch disease with bone compromise: atypical manifestation].

PubMed

Rodríguez C, Magdalena; Giachetto L, Gustavo; Cuneo E, Alejandro; Gutiérrez B, María del C; Shimchack R, Mario; Pírez G, M Catalina

2009-08-01

Fever, headache, myalgias and lymphadenopathy are characteristic manifestations of cat-scratch disease but other less common findings are described in 2 to 10% of cases. We report two children that presented with hepatosplenic abscesses and bone involvement. One child, had multiple areas of increased uptake in the bone scintigram with a positive serology (IgG > 1/256, IgM slightly positive). The second child had destruction of the L2 vertebral body that compromised the channel and right foramen as visualized by MRI. In both cases, bacilli were observed in the bone biopsy by Warthing-Starry stain.

Bone Health Monitoring in Astronauts: Recommended Use of Quantitative Computed Tomography [QCT] for Clinical and Operational Decisions

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Truskowski, P.

2010-01-01

This slide presentation reviews the concerns that astronauts in long duration flights might have a greater risk of bone fracture as they age than the general population. A panel of experts was convened to review the information and recommend mechanisms to monitor the health of bones in astronauts. The use of Quantitative Computed Tomography (QCT) scans for risk surveillance to detect the clinical trigger and to inform countermeasure evaluation is reviewed. An added benefit of QCT is that it facilitates an individualized estimation of bone strength by Finite Element Modeling (FEM), that can inform approaches for bone rehabilitation. The use of FEM is reviewed as a process that arrives at a composite number to estimate bone strength, because it integrates multiple factors.

Effect of vitamin D, calcium and multiple micronutrient supplementation on vitamin D and bone status in Bangladeshi premenopausal garment factory workers with hypovitaminosis D: a double-blinded, randomised, placebo-controlled 1-year intervention.

PubMed

Islam, Md Zahirul; Shamim, Abu Ahmed; Viljakainen, Heli T; Akhtaruzzaman, Mohammad; Jehan, Atia H; Khan, Habib Ullah; Al-Arif, Ferdaus Ahmad; Lamberg-Allardt, Christel

2010-07-01

Due to little outdoor activity and low dietary intake of vitamin D (VD), Bangladeshi low-income women are at risk for osteoporosis at an early age. The present study assessed the effect of VD, Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers. This placebo-controlled 1-year intervention randomly assigned 200 apparently healthy subjects (aged 16-36 years) to four groups: VD group, daily 10 microg VD; VD and Ca (VD-Ca) group, daily 10 microg VD+600 mg Ca; multiple micronutrient and Ca (MMN-Ca) group, 10 microg VD and other micronutrients+600 mg Ca; a placebo group. Serum 25-hydroxyvitamin D (S-25OHD), intact parathyroid hormone (S-iPTH), Ca, phosphate and alkaline phosphatase were measured. Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry. All measurements were made at baseline and at 12 months. Significantly (P < 0.001) higher S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention. Supplementation had an effect (P < 0.001) on S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group. Bone mineral augmentation increased at the femur in the supplemented groups. Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects. MMN-Ca may have analogous positive health implications with additional non-skeletal benefits.

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

PubMed

Blume, K G; Forman, S J

1992-12-01

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

Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy

PubMed Central

Eshleman, Nichole; Liu, Guangbo; McGrath, Kaitlyn; Parker, Roy; Buchan, J. Ross

2016-01-01

The nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3′ end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci (“TT foci”) are not stress granules but instead are a mRNP granule containing poly(A)+ mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3′ end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus. PMID:27251550

Evaluation of research topic evolution in psychiatry using co-word analysis

PubMed Central

Wu, Ying; Jin, Xing; Xue, Yunzhen

2017-01-01

Abstract With the rapid increase in the incidence of mental disorders and mental issues, psychiatry has become one of the fastest growing clinical medical disciplines. Development priorities and research foci in this field have evolved over different periods. All the articles in 10 psychiatric journals with the highest impact factors were selected from the Science Citation Index (SCI) in Web of Science from 2001 to 2015. The information visualization software Sci2 was used to conduct co-word and clustering analyses on these articles. The articles were divided into 3 periods: 2001 to 2005, 2006 to 2010, and 2011 to 2015. Each bibliographic record contained a title, author names, abstract, keywords, references, and other information. During the 3 periods between 2001 and 2015, child and adolescent psychiatry, major depression, schizophrenia, and prefrontal cortex were constant research foci. The brain and meta-analysis gradually became new research foci, although research on symptoms slowly decreased. Molecular genetics was also an area of interest. Using scientometrics technology to visualize research foci can provide us with new ideas and research methods. Co-word analysis for the preliminary exploration of research foci and developmental trends in psychiatry is helpful in finding developmental rules, choices of topics, and innovative research. Our study had some limitations. In the future, we should expand our research scope and use a variety of research methods to enrich our results. PMID:28640150

Evaluation of research topic evolution in psychiatry using co-word analysis.

PubMed

Wu, Ying; Jin, Xing; Xue, Yunzhen

2017-06-01

With the rapid increase in the incidence of mental disorders and mental issues, psychiatry has become one of the fastest growing clinical medical disciplines. Development priorities and research foci in this field have evolved over different periods.All the articles in 10 psychiatric journals with the highest impact factors were selected from the Science Citation Index (SCI) in Web of Science from 2001 to 2015. The information visualization software Sci was used to conduct co-word and clustering analyses on these articles. The articles were divided into 3 periods: 2001 to 2005, 2006 to 2010, and 2011 to 2015. Each bibliographic record contained a title, author names, abstract, keywords, references, and other information.During the 3 periods between 2001 and 2015, child and adolescent psychiatry, major depression, schizophrenia, and prefrontal cortex were constant research foci. The brain and meta-analysis gradually became new research foci, although research on symptoms slowly decreased. Molecular genetics was also an area of interest.Using scientometrics technology to visualize research foci can provide us with new ideas and research methods. Co-word analysis for the preliminary exploration of research foci and developmental trends in psychiatry is helpful in finding developmental rules, choices of topics, and innovative research. Our study had some limitations. In the future, we should expand our research scope and use a variety of research methods to enrich our results.

Piscine orthoreovirus (PRV) in red and melanised foci in white muscle of Atlantic salmon (Salmo salar).

PubMed

Bjørgen, Håvard; Wessel, Øystein; Fjelldal, Per Gunnar; Hansen, Tom; Sveier, Harald; Sæbø, Håkon Rydland; Enger, Katrine Bones; Monsen, Eirik; Kvellestad, Agnar; Rimstad, Espen; Koppang, Erling Olaf

2015-09-08

Melanised focal changes (black spots) are common findings in the white skeletal muscle of seawater-farmed Atlantic salmon (Salmo salar). Fillets with melanised focal changes are considered as lower quality and cause large economic losses. It has been suggested that red focal changes (red spots) precede the melanised focal changes. In the present work, we examined different populations of captive and wild salmon for the occurrence of both types of changes, which were investigated for the presence of different viruses by immunohistochemistry and RT-qPCR. The occurrence of red or melanised foci varied significantly between the populations, from none in wild fish control group, low prevalence of small foci in fish kept in in-house tanks, to high prevalence of large foci in farm-raised salmon. Large amounts of Piscine orthoreovirus (PRV) antigen were detected in all foci. No other viruses were detected. Red focal changes contained significantly higher levels of PRV RNA than apparently non-affected areas in white muscle of the same individuals. Some changes displayed a transient form between a red and melanised pathotype, indicating a progression from an acute to a chronic manifestation. We conclude that PRV is associated with the focal pathological changes in the white muscle of farmed Atlantic salmon and is a premise for the development of focal melanised changes.

FGF23 is elevated in multiple myeloma and increases heparanase expression by tumor cells

PubMed Central

Suvannasankha, Attaya; Tompkins, Douglas R.; Edwards, Daniel F.; Petyaykina, Katarina V.; Crean, Colin D.; Fournier, Pierrick G.; Parker, Jamie M.; Sandusky, George E.; Ichikawa, Shoji; Imel, Erik A.; Chirgwin, John M.

2015-01-01

Multiply myeloma (MM) grows in and destroys bone, where osteocytes secrete FGF23, a hormone which affects phosphate homeostasis and aging. We report that multiple myeloma (MM) cells express receptors for and respond to FGF23. FGF23 increased mRNA for EGR1 and its target heparanase, a pro-osteolytic factor in MM. FGF23 signals through a complex of klotho and a classical FGF receptor (FGFR); both were expressed by MM cell lines and patient samples. Bone marrow plasma cells from 42 MM patients stained positively for klotho, while plasma cells from 8 patients with monoclonal gammopathy of undetermined significance (MGUS) and 6 controls were negative. Intact, active FGF23 was increased 2.9X in sera of MM patients compared to controls. FGF23 was not expressed by human MM cells, but co-culture with mouse bone increased its mRNA. The FGFR inhibitor NVP-BGJ398 blocked the heparanase response to FGF23. NVP-BGJ398 did not inhibit 8226 growth in vitro but significantly suppressed growth in bone and induction of the osteoclast regulator RANK ligand, while decreasing heparanase mRNA. The bone microenvironment provides resistance to some anti-tumor drugs but increased the activity of NVP-BGJ398 against 8226 cells. The FGF23/klotho/heparanase signaling axis may offer targets for treatment of MM in bone. PMID:25944690

Osteomalacia: a case series of patients with atypical clinical orthopaedic presentations.

PubMed

Fok, A W M; Ng, T P

2010-12-01

Osteomalacia is uncommon in an affluent subtropical city like Hong Kong, where sunlight exposure is adequate and nutritional support is good. We present three patients who had osteomalacia with different presentations. A 74-year-old male with oncogenic osteomalacia presented with multiple bone pain. His biochemical markers returned to normal 4 days postoperatively after resection of a second toe giant cell tumour of tendon sheath. A 62-year-old woman with a history of liver problem and proximal muscle weakness was admitted with atraumatic fracture of the left distal humerus due to osteomalacia. An 81-year-old vegetarian woman with inadequate sun exposure complained of multiple bone pains. Subsequent investigation revealed dietary- and sunlight-deficient osteomalacia with multiple bony abnormalities including marked femur bowing.

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

PubMed Central

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

2016-01-01

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

Bone marrow derived stem cells in joint and bone diseases: a concise review.

PubMed

Marmotti, Antonio; de Girolamo, Laura; Bonasia, Davide Edoardo; Bruzzone, Matteo; Mattia, Silvia; Rossi, Roberto; Montaruli, Angela; Dettoni, Federico; Castoldi, Filippo; Peretti, Giuseppe

2014-09-01

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.

Traumatic fracture in a healthy man: benign or pathologic?

PubMed

Nora, Elizabeth H; Kennel, Kurt A; Christian, Rose C

2006-01-01

To describe the challenge of determining the correct diagnosis in a healthy adult male patient with a recent femoral fracture and a history of multiple bone fractures. We present clinical, radiologic, laboratory, and histopathologic details in a patient with a history of recurrent fractures associated with minimal trauma. Moreover, the various types of osteopetrosis are reviewed. A 34-year-old African American man was in his usual state of good health when he fell hard on concrete. Immediately after the fall, he was able to bear weight, although pain prompted him to seek medical care. Besides a personal history of multiple fractures, he had no other medical problems. He had never smoked, denied illicit drug use, and had no family history of bone disorders or recurrent fractures. Findings on physical examination were unremarkable. Radiography disclosed an incomplete femoral fracture and osteosclerosis. Bone survey revealed diffuse, symmetric osteosclerosis of both the axial and the appendicular skeleton. The long bones showed areas of almost complete obliteration of the medullary canal, along with prominent hyperostosis. Additionally, a "bone-within-bone" appearance to the thickened endosteum was noted. A bone scan demonstrated numerous areas of symmetric radiotracer uptake. Laboratory analyses were unremarkable, including a complete blood cell count, electrolytes, serum protein electrophoresis, thyrotropin, and parathyroid hormone. Total alkaline phosphatase was mildly elevated at 162 U/L (normal range, 35 to 130). Seven needles were broken during attempts to perform a bone biopsy. Histologic examination showed normal bone marrow with "woven" bone and areas of primary spongiosa within mature osteoid. Autosomal dominant osteopetrosis type 2 was diagnosed on the basis of his clinical presentation and the radiologic and pathologic findings. The preliminary diagnosis for this patient's condition was Paget's disease, and determining the correct diagnosis of osteopetosis prevented the administration of inappropriate therapy. In addition, this case report reminds the clinician that genetic disease may manifest in adulthood.

PET/MRI of metabolic activity in osteoarthritis: A feasibility study.

PubMed

Kogan, Feliks; Fan, Audrey P; McWalter, Emily J; Oei, Edwin H G; Quon, Andrew; Gold, Garry E

2017-06-01

To evaluate positron emission tomography / magnetic resonance imaging (PET/MRI) knee imaging to detect and characterize osseous metabolic abnormalities and correlate PET radiotracer uptake with osseous abnormalities and cartilage degeneration observed on MRI. Both knees of 22 subjects with knee pain or injury were scanned at one timepoint, without gadolinium, on a hybrid 3.0T PET-MRI system following injection of 18 F-fluoride or 18 F-fluorodeoxyglucose (FDG). A musculoskeletal radiologist identified volumes of interest (VOIs) around bone abnormalities on MR images and scored bone marrow lesions (BMLs) and osteophytes using a MOAKS scoring system. Cartilage appearance adjacent to bone abnormalities was graded with MRI-modified Outerbridge classifications. On PET standardized uptake values (SUV) maps, VOIs with SUV greater than 5 times the SUV in normal-appearing bone were identified as high-uptake VOI (VOI High ). Differences in 18 F-fluoride uptake between bone abnormalities, BML, and osteophyte grades and adjacent cartilage grades on MRI were identified using Mann-Whitney U-tests. SUV max in all subchondral bone lesions (BML, osteophytes, sclerosis) was significantly higher than that of normal-appearing bone on MRI (P < 0.001 for all). Of the 172 high-uptake regions on 18 F-fluoride PET, 63 (37%) corresponded to normal-appearing subchondral bone on MRI. Furthermore, many small grade 1 osteophytes (40 of 82 [49%]), often described as the earliest signs of osteoarthritis (OA), did not show high uptake. Lastly, PET SUV max in subchondral bone adjacent to grade 0 cartilage was significantly lower compared to that of grades 1-2 (P < 0.05) and grades 3-4 cartilage (P < 0.001). PET/MRI can simultaneously assess multiple early metabolic and morphologic markers of knee OA across multiple tissues in the joint. Our findings suggest that PET/MR may detect metabolic abnormalities in subchondral bone, which appear normal on MRI. 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1736-1745. © 2016 International Society for Magnetic Resonance in Medicine.

Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET/CT) Findings in an Unusual Case of Multiple Myeloma Presenting with a Large Extra-Axial Intracranial Mass.

PubMed

Ayaz, Sevin; Ayaz, Ümit Yaşar

2016-01-01

We aimed to present unusual cranial FDG PET/CT findings of a 56-year-old female with multiple myeloma (MM). Plain CT images revealed a lytic lesion in the right parietal bone, filled with an oval-shaped, large, extra-axial, extradural, intracranial mass which measured 75×75×40 mm and had smooth borders. The right parietal lobe was compressed by the mass. The maximum standardized uptake value (SUV max ) of the mass lesion was 8.94 on FDG PET/CT images. Multiple lytic lesions with an increased uptake were also detected in other calvarial bones, in several vertebras and in the proximal left femur. After seven months, a control FDG PET/CT following radiotherapy and chemotherapy revealed almost complete regression of the right parietal extra-axial mass lesion. The number, size and metabolism of lytic lesions in other bones also decreased. FDG PET/CT was useful for an initial evaluation of MM lesions and was effective in monitoring the response of these lesions to therapy.

Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine.

PubMed

Li, Guanqun; Liu, Xujun; Du, Qian; Gao, Mei; An, Jing

2015-08-01

The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. © 2015 by the Society for Experimental Biology and Medicine.

Mesenchymal stem cells for bone repair and metabolic bone diseases.

PubMed

Undale, Anita H; Westendorf, Jennifer J; Yaszemski, Michael J; Khosla, Sundeep

2009-10-01

Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.

Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients

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

MacLennan, I.; Keys, H.M.; Evarts, C.M.

1984-01-01

Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible onmore » postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized.« less

Bone Plating in Patients with Type III Osteogenesis Imperfecta: Results and Complications

PubMed Central

Enright, William J; Noonan, Kenneth J

2006-01-01

The results of bone plating in four children (6 femurs, 2 tibias) with osteogenesis imperfecta type III were analyzed. Average age at time of operation was 44 months. In three of the femurs, multiple platings were performed for a total of 13 bone platings in the eight bones studied. Average time to revision following plating was 27 months. Indications for revision included fracture (6), deformity (3), hardware failure (3), and nonunion (1). Other complications included one case of compartment syndrome. All eight bones were ultimately revised to elongating intramedullary Bailey-Dubow rods. Bone plating in skeletally immature patients with osteogenesis imperfecta does not provide better outcome than elongating rods. Complications from bone plating leading to revision, such as refracture or hardware failure, are higher than in those children managed with elongating rods, as previously reported in the literature. PMID:16789446

Animal Models of Bone Metastasis

PubMed Central

Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

2015-01-01

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

Extension Personnel's Self-Esteem and Workplace Relationships: Implications for Job Satisfaction and Affective Organizational Commitment Foci

ERIC Educational Resources Information Center

Ladebo, Olugbenga Jelil; Olaoye, Olalekan Jacob; Adamu, Comfort Oyekale

2008-01-01

This study proposes relationships between job satisfaction, affective commitment (organization, supervisor and workgroup), and exchange relations with supervisor, organization and workgroup members among extension personnel. Perceived self-esteem (SE) is hypothesized to moderate relations between the social exchange foci and the corresponding…

Bone-seeking TRAP conjugates: surprising observations and their implications on the development of gallium-68-labeled bisphosphonates

PubMed Central

2012-01-01

Background Bisphosphonates possess strong affinity to bone. 99mTc bisphosphonate complexes are widely used for bone scintigraphy. For positron emission tomography (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly desirable. Findings Two trimeric bisphosphonate conjugates of the triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga-68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers show bone uptake and, thus, are suitable for PET bone imaging. Surprisingly, Ga-71 nuclear magnetic resonance data prove that Ga(III) is not located in the chelating cavity of TRAP and must therefore be bound by the conjugated bisphosphonate units. Conclusion The intrinsic Ga-68 chelating properties of TRAP are not needed for Ga-68 PET bone imaging with TRAP-bisphosphonate conjugates. Here, TRAP serves only as a trimeric scaffold. For preparation of Ga-68-based bone seekers for PET, it appears sufficient to equip branched scaffolds with multiple bisphosphonate units, which serve both Ga-68-binding and bone-targeting purposes. PMID:22464278

Efficacy of bone substitute material in preserving volume when placing a maxillary immediate complete denture: study protocol for the PANORAMIX randomized controlled trial.

PubMed

Rignon-Bret, Christophe; Hadida, Alain; Aidan, Alexis; Nguyen, Thien-Huong; Pasquet, Gerard; Fron-Chabouis, Helene; Wulfman, Claudine

2016-05-20

Bone preservation is an essential issue in the context of last teeth extraction and complete edentulism. The intended treatment, whether a complete denture or an implant placement, is facilitated with a voluminous residual ridge. Bone resorption after multiple extractions has not been as well studied as the bone resorption that occurs after the extraction of a single tooth. Recent advances in bone substitute materials have revived this issue. The purpose of this study is to evaluate the interest in using bone substitute material to fill the socket after last teeth extraction in a maxillary immediate complete denture procedure compared with the conventional protocol without socket filling. A randomized, controlled, clinical trial was designed. The 34 participants eligible for maxillary immediate complete denture were divided into two groups. Complete dentures were prepared despite persistence of the last anterior teeth. The control group received a conventional treatment including denture placement immediately after extractions. In the experimental group, in addition to the immediate denture placement, a xenograft bone-substitute material (Bio-Oss Collagen®) was placed in the fresh sockets. The primary outcome of the study is to compare mean bone ridge height loss 1 year after maxillary immediate complete denture placement, with or without bone-substitute material, in incisor and canine sockets. The secondary outcomes are to compare the average bone ridge height and width loss for each extraction site. An original quantitative evaluation method using cone beam computed tomography was designed for reproducible measurements, with a radio-opaque denture duplicate. Two independent operators perform the radiologic measurements. The immediate complete denture technique limits bone resorption in multiple extraction situations and thus allows better denture retention and better options for implant placement. To compare the benefit of using any bone socket-filling material, we proposed a quantitative evaluation protocol of resorption in the specific case of the last anterior maxillary teeth extraction with immediate denture placement. ClinicalTrials.gov, NCT02120053 . Registered on 18 April 2014.

Pre-operative factors indicating risk of multiple operations versus a single operation in women undergoing surgery for screen detected breast cancer.

PubMed

O'Flynn, E A M; Currie, R J; Mohammed, K; Allen, S D; Michell, M J

2013-02-01

We aim to identify preoperative factors at diagnosis which could predict whether women undergoing wide local excision (WLE) would require further operations. 1593 screen-detected invasive and non-invasive breast cancers were reviewed. Age, presence of ductal carcinoma in situ (DCIS), invasive cancer size on mammography, mammographic sign, tumour type, grade and confidence of the radiologist in malignancy were compared. 83%(1315/1593) of women had a WLE. Of these, 70%(919/1315) had a single operation, and 30%(396/1315) multiple operations. These included repeat WLE to clear margins (60%(238/396)), mastectomy (34%(133/396)) and axillary dissection (6%(25/396)). The presence of mammographic microcalcification, lobular carcinoma and grade 2 malignancy on core biopsy were independent risk factors for multiple operations on multivariate analysis. Women with mammographic DCIS >30 mm were 3.4 times more likely to undergo repeat surgery than those with smaller foci. The multidisciplinary team should pay particular attention to these factors when planning surgery. Copyright © 2012 Elsevier Ltd. All rights reserved.