bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification
Authors: Williams Justin N , Kambrath Anuradha Valiya , Patel Roshni B , Kang Kyung Shin , Mével Elsa , Li Yong , Cheng Ying-Hua , Pucylowski Austin J , Hassert Mariah A , Voor Michael J , Kacena Melissa A , Thompson William R , Warden Stuart J , Burr David B , Allen Matthew R , Robling Alexander G , Sankar Uma 
Published: January 2018

ABSTRACT

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO-609 resulted in enhanced Indian hedgehog signaling, paired-related homeobox (PRX1)-positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO-609–treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO-609–treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO-609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones. © 2018 American Society for Bone and Mineral Research.
Functional Performances on Admission Predict In-Hospital Falls, Injurious Falls, and Fractures in Older Patients: A Prospective Study
Authors: Hars Mélany , Audet Marie-Claude , Herrmann François , De Chassey Jean , Rizzoli René , Reny Jean-Luc , Gold Gabriel , Ferrari Serge , Trombetti Andrea 
Published: January 2018

ABSTRACT

Falls are common among older inpatients and remain a great challenge for hospitals. Despite the relevance of physical impairments to falls, the prognostic value of performance-based functional measures for in-hospital falls and injurious falls remains unknown. This study aimed to determine the predictive ability and accuracy of various functional tests administered at or close to admission in a geriatric hospital to identify in-hospital fallers and injurious fallers. In this prospective study, conducted in a geriatric hospital in Geneva, Switzerland, 807 inpatients (mean age 85.0 years) were subjected to a battery of functional tests administered by physiotherapists within 3 days (interquartile range 1 to 6) of admission, including Short Physical Performance Battery (SPPB), simplified Tinetti, and Timed Up and Go tests. Patients were prospectively followed up for falls and injurious falls until discharge using mandatory standardized incident report forms and electronic patients’ records. During a median length of hospital stay of 23 days (interquartile range 14 to 36), 329 falls occurred in 189 (23.4%) patients, including 161 injurious falls of which 24 were serious. In-hospital fallers displayed significantly poorer functional performances at admission on all tests compared with non-fallers (p &lt; 0.001 for all). In multivariate analysis controlling for age, sex, previous falls, and fall as cause of admission, poorer functional performances on all functional tests predicted in-hospital falls and injurious falls (p &lt; 0.001 for all). The SPPB only significantly predicted serious injurious falls (adjusted odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.60–0.96) and fractures (adjusted OR = 0.76; 95% CI 0.59–0.98). In conclusion, poor functional performances, as assessed by SPPB, are independent predictors of in-hospital falls, injurious falls, and fractures in patients admitted to a geriatric hospital. These findings should help to design preventive strategies for in-hospital falls and support the adoption of objective performance-based functional measures into routine hospital practice. © 2018 American Society for Bone and Mineral Research.
Future Osteoporotic Fracture Risk Related to Lumbar Vertebral Trabecular Attenuation Measured at Routine Body CT
Authors: Lee Scott J , Graffy Peter M , Zea Ryan D , Ziemlewicz Timothy J , Pickhardt Perry J 
Published: January 2018

ABSTRACT

We sought to determine if vertebral trabecular attenuation values measured on routine body computed tomography (CT) scans obtained for a variety of unrelated indications can predict future osteoporotic fractures at multiple skeletal sites. For this Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)-approved retrospective cohort study, trabecular attenuation of the first lumbar vertebra was measured in 1966 consecutive older adults who underwent chest and/or abdominal CT at a single institution over the course of 1 year. New pathologic fragility fractures that occurred after a patient's CT study date were identified through an electronic health record database query using International Classification of Diseases (ICD)-9 codes for vertebral, hip, and extremity fractures. Univariate and multivariate Cox proportional hazards regression were performed to determine the effect of L1 trabecular attenuation on fracture-free survival. Age at CT, sex, and presence of a prior fragility fracture were included as confounders in multivariate survival analysis. Model discriminative capability was assessed through calculation of an optimism-corrected concordance index. A total of 507 patients (mean age 73.4 ± 6.3 years; 277 women, 230 men) were included in the final analysis. The median post-CT follow-up interval was 5.8 years (interquartile range 2.1–11.0 years). Univariate analysis showed that L1 attenuation values ≤90 Hounsfield units (HU) are significantly associated with decreased fracture-free survival (p &lt; 0.001 by log-rank test). After adjusting for age, sex, prior fracture, glucocorticoid use, bisphosphonate use, chronic kidney disease, tobacco use, ethanol abuse, cancer history, and rheumatoid arthritis history, multivariate analysis demonstrated a persistent modest effect of L1 attenuation on fracture-free survival (hazard ratio [HR] = 0.63 per 10-unit increase; 95% confidence interval [CI] 0.47–0.85). The model concordance index was 0.700. Ten-year probabilities for major osteoporosis-related fractures straddled the treatment threshold for most subcohorts over the observed L1 HU range. In conclusion, for patients undergoing body CT scanning for any indication, L1 vertebral trabecular attenuation is a simple measure that, when ≤90 HU, identifies patients with a significant decrease in fracture-free survival. © 2018 American Society for Bone and Mineral Research.
Adsorption of phenol from aqueous solutions using interlayer modified titanate nanotubes
Authors: Hu Lihe , Zhang Jixiang , Li Nian , Zhang Shudong , Chen Fa , Ji Bo , Li Haifeng , Wang Zhenyang 
Published: January 2018

AbstractBACKGROUNDLayered titanate nanostructures have long been studied as efficient adsorbents for different kinds of pollutants such as heavy metals and dye cations. As to the electro‐neutral and anionic organic pollutants, titanates show relatively low adsorption capacity due to a negatively charged surface and lack of organophilic affinity. This research focuses on the interlayer modification of titanate nanotubes for adsorption of this kind of organic pollutants. Phenol was chosen as a representative target.RESULTSTwo surfactants, hexadecyl trimethyl ammonium bromide (HTAB) and dodecyl dimethyl benzyl ammonium bromide (DDBAB), were chosen as organic modifier for the interlayer modification. Detailed characterization proved that surfactant molecules were intercalated into the interlayer and surface properties of titanates were successfully modified. Adsorption behavior of phenol was then systematically investigated. Results show that DDBAB modified titanates are efficient phenol adsorbents, possessing better performance than HTAB modified titanates. The high adsorption capacity is attributed to the special structure of titanates and the affinity between phenyl groups in DDBAB and phenol. Subsequently, thermally induced phase change of spent adsorbents led to complete regeneration.CONCLUSIONInterlayer modified titanate nanotubes were efficient phenol adsorbents with a maximum adsorption capacity of 226.24 mg g‐1. Complete regeneration of spent adsorbents was also achieved. © 2018 Society of Chemical Industry
Noninvasive Studies of Kupffer Cells In Situ by Magnetometry
Authors: Gehr Peter , Brain Joseph D , Bloom Steven B 
Published: January 2018

Abstract
Magnetic iron oxide (gamma-Fe2O3) particles were injected intravenously into four male New Zealand white rabbits. Most of these particles were phagocytized by the Kupffer cells. When the animal was placed in a magnetic field, the particles in the liver became magnetized and aligned. After removal of the external magnetizing field, the particles collectively produced a remanent magnetic field which was measured at the body surface. The strength of this field was proportional to the amount of magnetic particles present in the liver; sequential measurements thus allowed us to describe their disappearance from the liver. After each magnetization, the remanent field rapidly decayed due to particle rotation (relaxation). Since the particles were confined in phagosomes or secondary lysosomes we conclude that movements of these organelles due to cytoplasmic motion caused relaxation. Magnetic particles might therefore serve as probes for cytoplasmic motility of Kupffer cells in situ.
Characterization of Rabbit Neutrophil Membrane Proteins. A 140K Major Membrane Protein is the Predominant Con A-Binding Protein
Authors: Williams Deborah J , Becker Elmer L 
Published: January 2018

Abstract
The major plasma membrane proteins of rabbit neutrophils were characterized by SDS-PAGE, surface iodination, 125l-concanavalin A binding, and detergent extraction. Neutrophil membranes were prepared which lacked significant intracellular contamination with good retention of protease-sensitive proteins. The major protein and predominant Con A-binding protein was as surface exposed, 140,000 D (gp 140) protein which was solubilized by nonionic detergents but not low ionic strength. Actin and myosin but not other cytosol proteins were prominently associated with the isolated membrane particularly in a Triton-insoluble form.
Membranes were also prepared from surface-iodinated neutrophils previously stimulated with a chemotactic peptide or degranulated. The granule membrane enzyme alkaline phosphatase was incorporated into the plasma membrane fraction of degranulated neutrophils. However, the membrane proteins in the different membrane preparations were identical on SDS-PAGE and autoradiography. Therefore, using these techniques, no major alterations in protein composition of the plasma membrane could be detected following stimulation or degranulation of rabbit neutrophils.
Concomitant Induction of an Inflammatory Response and Immunosuppression by an Extract From Listeria monocytogenes
Authors: Otokunefor T V , Galsworthy S B 
Published: January 2018

Abstract
An immunosuppressive agent (ISA) present in an aqueous extract from Listeria monocytogenes diminished the immune response in vivo to subsequently injected heterologous antigen. Intraperitoneal injection of ISA induced an inflammatory response and activation of the reticuloendothelial system, both of which coincided with the period of immune hyporesponsiveness. Mice treated with ISA exhibited increased accumulation of labelled antigen to phagocytic peritoneal cells but decreased delivery of labelled antigen to the spleen. Both delivery of antigen to spleen and the immune response could be improved by injecting either ISA or antigen or both intravenously, or by increasing the dose of antigen. The response of ISA-treated animals could also be improved by intraperitoneal injection of latex beads, colloidal carbon, or carrageenan shortly (60 min) before immunization. Spleen cells from ISA-treated mice adoptively transferred to irradiated syngeneic recipients were able to mount a normal immune response. These results suggest that ingestion of antigen by the enlarged population of phagocytes in peritoneal cavities of ISA-treated mice prevented antigen delivery to the spleen and was partly responsible for the observed immunosuppression.
The Effect of Temperature and Starvation on the Clearance of Bacteria From the Bloodstream of Rainbow Trout (Salmo gairdneri Richardson)
Authors: Ferguson H W , Claxton M J , Lesperance J 
Published: January 2018

Abstract
The blood clearance of 51Cr-labeled heat-killed Salmonella pullorum was generally biphasic and exponential for each phase. Starvation had little significant effect on this pattern, although the rate of first phase clearance was probably slower. Raising the water temperature from 8°C to 18°C enhanced the rate of clearance of the second phase to almost exactly double that at 8°C. At 18 hr postinoculation, the spleen contained much more radioactivity per gm than any other tissue. This finding is in marked contrast to earlier work that showed that at 1 hr postinoculation, the kidney contained the most, and it suggests that redistribution of bacteria occurred. The most distinct effect of temperature stress on tissue localization of bacteria was in the heart: A rising temperature stress caused increased numbers of bacteria to localize within the heart. Less clear-cut changes were also seen in other tissues with different treatments.
With the possible exception of starvation effecting a slower first phase clearance rate, we have been unable to demonstrate that the vascular clearance mechanisms, including the reticuloendothelial system, are significantly compromised by raising the water temperature or by starvation.
Human Monocyte to Macrophage Differentiation In Vitro: Characterization and Mechanisms of the Increased Antibody-Dependent Cytotoxicity Associated With Differentiation
Authors: Sagone Arthur L , Rinehart John J 
Published: January 2018

Abstract
Human monocyte-to-macrophage differentiation in vitro is associated with marked enhancement in the capacity to bind and lyse antibody-opsonized red blood cells (rbc). We previously demonstrated that this was due in part to an increased number of Fc receptors. The current study further characterized the mechanism of this enhanced macrophage as antibody-dependent cellular cytotoxicity (ADCC). We observed that 1) macrophages but not monocytes lysed “innocent bystander” rbc as well as opsonized rbc; 2) macrophages exhibited an increased hexose monophosphate shunt activity compared to monocytes; 3) macrophage produced H2O2 but not OH·; and 4) macrophage lyses of opsonized rbc were 80% O2 dependent. We conclude that human monocyte-to-macrophage maturation in vitro is associated with an enhanced O2-dependent cytotoxic mechanism normally present in monocytes. The enhanced H2O2 production noted in macrophages may reflect an increased generation of several other reactive oxygen species in these cells. One of these oxygen radicals may be the mediator of the enhanced macrophage cytotoxicity and of the “innocent bystander” phenomenon observed.
Purification of Murine Macrophage Cytotoxin (MCT)
Authors: Klostergaard Jim , Reidarson Thomas H , Granger Gale A 
Published: January 2018

Abstract
Macrophage cytotoxin (MCT) can be induced from peritoneal exudate macrophage monolayers (PEMM) obtained from thioglycollate-treated mice, by exposure of PEMM to lipopolysaccharide (LPS) or to double-stranded polyinosinic: poly-cytidylic acid (poly-l:poly-C). MCT is highly labile even upon storage at 4°C, and is irreversibly denatured by isolectricfocusing, polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate (SDS), or by exposure to ethylene glycol. α-MCT [150,000 daltons (d)] has been highly purified (2,000- to 5,000-fold) from serum-free, PEMM supernatants by a scheme of concentration, molecular sieving on Ultrogel AcA 44, negative hydrophobic affinity chromatography on benzyl-agarose, and ion exchange chromatography on aminoethyl-agarose. The scheme results in high yield of MCT, in part because of the rapidity with which the labile toxin is manipulated due to the tandemization of the chromatographic steps.
Involution of the Chicken Bursa of Fabricius: A Light Microscopic Study With Special Reference to Transport of Colloidal Carbon in the Involuting Bursa
Authors: Naukkarinen Anita , Sorvari Tapani E 
Published: January 2018

Abstract
The involution of the bursa of Fabricius in White Leghorn chickens and the transport of colloidal carbon in the involuting bursa were studied on light microscopy. In chickens, from newly hatched to 23.5 weeks of age, the bursa was weighed, its histology was described, and the mitoses in the cortical and medullary compartments of the lymphoid follicles were counted.
Decrease in bursal weight and in the number of mitoses were observed between 10 and 16 weeks of age. During week 17.5, the follicle-associated epithelium began to lose its endocytic capability, and mucin droplets appeared in the follicular medulla initiating the large mucoid cysts that were seen in the later phases of involution. The involutionary process was almost completed by week 23.5, when the bursa appeared as a fibrotic residue without intact lymphoepithelial structures. The particulate tracer used, colloidal carbon, was not observed to be transported to other organs from the bursa.
The present study gives further support to the idea that after completing its central immune function in 6 weeks [21] the bursa, as estimated histologically, still possesses capacity to function like a peripheral lymphoid organ until 16 weeks of age.
Macrophage Microtubules: An Optimized Method for the Assay of Tubulin Concentration and State of Polymerization in Macrophages
Authors: Seger Medy , Pick Edgar 
Published: January 2018

Abstract
We describe a method for the assay of total tubulin content and the tubulin dimer/polymer ratio in cultured macrophages (MPs). The assay is based on the specific binding of [3H]colchicine to tubulin dimer units and on the separation of free and tubulin-complexed [3H]colchicine on diethylaminoethyl (DEAE)-cellulose filters. The native state of microtubules (MTs) was conserved by suspending the cells in a microtubule-stabilizing solution specifically adapted for use with MPs and by disrupting the cells under carefully chosen conditions. Intact MTs were isolated from the cell homogenate by centrifugation at 150,000 × g and were subsequently depolymerized. [3H]Colchicine binding assays were performed on both the supernatant fraction, containing the pool of soluble tubulin, and on the deploymerized MTs. By using this method, we examined the influence of low temperature and of a number of agents known to affect MP function, on the tubulin dimer/polymer ratio in guinea pig peritoneal MPs. The results of the biochemical assay correlated well with the published information, derived by morphologic and functional approaches, on the effect of cold and of these agents on MTs in phagocytic cells.
The Proliferation Kinetics of Pulmonary Alveolar Macrophages
Authors: Coggle J E , Tarling J D 
Published: January 2018

Abstract
In this study the proliferation kinetics of pulmonary alveolar macrophages (PAMs) are determined using [3H]thymidine labeling, flow cytofluorimetry, metaphase arrest, and the percentage of labeled mitoses. The demonstration of in situ PAM proliferation is demonstrated beyond doubt. Comparison of the turnover time, calculated from cell kinetic parameters, with the experimentally determined migration times shows that the contribution proliferating PAMs make to their own population size is significant. Indeed, a strong case may be made to show that some 70% of the PAM population is produced by intra-alveolar divisions of “free” PAMs.
Function of Human Alveolar Macrophages From Normal Volunteers and Cigarette Smokers: Effect of Cystic Fibrosis Serum
Authors: Thomassen Mary Jane , Demko Catherine A , Winnie Glenna B , Sherman James M 
Published: January 2018

Abstract
Previous studies demonstrated that serum from cystic fibrosis (CF) patients specifically inhibited Pseudomonas phagocytosis by both normal and CF alveolar macrophages. In the present study, inhibition of Pseudomonas aeruginosa phagocytosis by CF serum was significantly less on macrophages from heavy smokers than on cells from normal volunteers (P &lt; 0.01). Normal volunteer cells cultured for 10 days were also less affected by CF serum as compared to cells cultured for 24 hours from the same individual (P &lt; 0.01). Altered morphology (increased size and spreading on glass surfaces) and increased intracellular glycosidases of these cells were suggestive of a difference in the state of activation compared to normal cells. Macrophages from heavy smokers and 10-day cultures from normal volunteers were inhibited by heated CF serum, suggesting that complement-mediated opsonization was responsible for attachment or ingestion of P. aeruginosa in CF serum by these macrophages.
Functional Resistance of Inflammatory Macrophages to Methotrexate In Vitro
Authors: Zeller Janice M , Gudewicz Paul W 
Published: January 2018

Abstract
The purpose of this study was to evaluate the effects of high and low therapeutic doses of methotrexate (MTX) on macrophage metabolism and function in vitro. Monolayers of elicited rat peritoneal macrophages (PM) were exposed to a wide range of MTX concentrations (10–8 M–10–3 M) for 24 or 48 hr and macrophage RNA and protein metabolism were evaluated by the incorporation of [3H]5-uridine and [14C]1-leucine, respectively, into trichloroacetic acid (TCA)-precipitable material. Macrophage functional activity was examined by measuring the uptake of [14C]Pseudomonas aeruginosa to assess phagocytosis and the release of 51Cr from antibody-coated [51Cr]sheep red blood cells (SRBC) to assess antibody-dependent cell-mediated cytotoxicity. Following a 24-hr incubation with 10–3 M MTX, incorporation of [3H]5-uridine into PM monolayers was enhanced 79% when compared to control monolayers (p &lt; 0.005). Washout studies revealed that the stimulation of uridine incorporation was no longer observed by 24 hr following the removal of MTX from the culture medium. Incubation with 10–3 M MTX for 48 hr returned uridine incorporation to control levels, although leucine incorporation into protein was reduced by 22% (p &lt; 0.01). The depression in leucine incorporation in the presence of 10–3 M MTX was not reversed after the removal of MTX from the culture medium. Uptake of [14C]P. aeruginosa was not altered following a 24- or 48-hr incubation with either 10–7 M or 10–3 M MTX. Similarly, [51Cr]SRBC cytolysis was not affected by a 2-hr preincubation with and continuous exposure to between 10–8 M and 10–3 M MTX. These results demonstrate that incubation of inflammatory macrophages with clinically high doses of MTX can alter macrophage RNA and protein metabolism without producing demonstrable changes in macrophage functional activity.