Intra-articular osteoid osteoma of the calcaneus: a case report and review

AbstractOsteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis

In vivo FRET analyses reveal a role of ATP hydrolysis–associated conformational changes in human P-glycoprotein

P-glycoprotein (P-gp; also known as MDR1 or ABCB1) is an ATP-driven multidrug transporter that extrudes various hydrophobic toxic compounds to the extracellular space. P-gp consists of two transmembrane domains (TMDs) that form the substrate translocation pathway and two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP. At least two P-gp states are required for transport. In the inward-facing (pre-drug transport) conformation, the two NBDs are separated, and the two TMDs are open to the intracellular side; in the outward-facing (post-drug transport) conformation, the NBDs are dimerized, and the TMDs are slightly open to the extracellular side. ATP binding and hydrolysis cause conformational changes between the inward-facing and the outward-facing conformations, and these changes help translocate substrates across the membrane. However, how ATP hydrolysis is coupled to these conformational changes remains unclear. In this study, we used a new FRET sensor that detects conformational changes in P-gp to investigate the role of ATP binding and hydrolysis during the conformational changes of human P-gp in living HEK293 cells. We show that ATP binding causes the conformational change to the outward-facing state and that ATP hydrolysis and subsequent release of γ-phosphate from both NBDs allow the outward-facing state to return to the original inward-facing state. The findings of our study underscore the utility of using FRET analysis in living cells to elucidate the function of membrane proteins such as multidrug transporters

Intra-articular osteoid osteoma of the calcaneus: A case report and review

Osteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis. © 2016 The Authors.Embargo Period 12 month

Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption

AbstractThe biological role of phosphatidylinositol (PI)-3 kinase was examined in osteoclast-like multinucleated cells (OCLs) formed in co-cultures of mouse osteoblastic cells and bone marrow cells. The expression of PI-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit-forming activity on dentine slices and disrupted a ringed structure of F-actin-containing dots (an actin ring) in OCLs in a dose-dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI-3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI-3 kinase is important in osteoclastic bone resorption

ABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol trafficking

Large transporter protein linked to schizophrenia. 京都大学プレスリリース. 2021-01-07.ABCA13の異常によるコレステロール輸送障害が統合失調症を引き起こすことを解明. 京都大学プレスリリース. 2021-01-08.ATP-binding cassette subfamily A member 13 (ABCA13) is predicted to be the largest ABC protein, consisting of 5, 058 amino acids and a long N-terminal region. Mutations in the ABCA13 gene were reported to increase the susceptibility to schizophrenia, bipolar disorder and major depression. However, little is known about the molecular functions of ABCA13 or how they associate with psychiatric disorders. Here, we examined the biochemical activity of ABCA13 using HEK293 cells transfected with mouse ABCA13. The expression of ABCA13 induced the internalization of cholesterol and gangliosides from the plasma membrane to intracellular vesicles. Cholesterol internalization by ABCA13 required the long N-terminal region and ATP hydrolysis. To examine the physiological roles of ABCA13, we generated Abca13 KO mice using CRISPR/Cas and found that these mice exhibited deficits of prepulse inhibition. Vesicular cholesterol accumulation and synaptic vesicle endocytosis were impaired in primary cultures of Abca13 KO cortical neurons. Furthermore, mutations in ABCA13 gene associated with psychiatric disorders disrupted the protein’s subcellular localization and impaired cholesterol trafficking. These findings suggest that ABCA13 accelerates cholesterol internalization by endocytic retrograde transport in neurons and that loss-of-this function is associated with the pathophysiology of psychiatric disorders

Hard X-ray nanofocusing using adaptive focusing optics based on piezoelectric deformable mirrors

An adaptive Kirkpatrick-Baez mirror focusing optics based on piezoelectric deformable mirrors was constructed at SPring-8 and its focusing performance characteristics were demonstrated. By adjusting the voltages applied to the deformable mirrors, the shape errors (compared to a target elliptical shape) were finely corrected on the basis of the mirror shape determined using the pencil-beam method, which is a type of at-wavelength figure metrology in the X-ray region. The mirror shapes were controlled with a peak-to-valley height accuracy of 2.5 nm. A focused beam with an intensity profile having a full width at half maximum of 110 × 65 nm (V × H) was achieved at an X-ray energy of 10 keV.Takumi Goto, Hiroki Nakamori, Takashi Kimura, Yasuhisa Sano, Yoshiki Kohmura, Kenji Tamasaku, Makina Yabashi, Tetsuya Ishikawa, Kazuto Yamauchi, and Satoshi Matsuyama, "Hard X-ray nanofocusing using adaptive focusing optics based on piezoelectric deformable mirrors", Review of Scientific Instruments 86, 043102 (2015) https://doi.org/10.1063/1.4916617

Experimental and simulation study of undesirable short-period deformation in piezoelectric deformable x-ray mirrors

To construct adaptive x-ray focusing optics whose optical parameters can be varied while performing wavefront correction, ultraprecise piezoelectric deformable mirrors have been developed. We computationally and experimentally investigated undesirable short-period deformation caused by piezoelectric actuators adhered to the substrate during mirror deformation. Based on the results of finite element method analysis, shape measurements, and the observation of x-ray reflection images, a guideline is developed for designing deformable mirrors that do not have short-period deformation errors. © 2012 American Institute of Physics.Hiroki Nakamori, Satoshi Matsuyama, Shota Imai, Takashi Kimura, Yasuhisa Sano, Yoshiki Kohmura, Kenji Tamasaku, Makina Yabashi, Tetsuya Ishikawa, and Kazuto Yamauchi, "Experimental and simulation study of undesirable short-period deformation in piezoelectric deformable x-ray mirrors", Review of Scientific Instruments 83(5), 053701 (2012) https://doi.org/10.1063/1.4709499

Stimulatory Effects of CO2 Laser, Er:YAG Laser and Ga-Al-As Laser on Exposed Dentinal Tubule Orifices

We investigated the effects of lasers irradiation on the exposed dentinal tubule. Human tooth specimens with exposed dentinal tubule orifices were used. Three types of lasers (CO2 laser, Er:YAG laser and Ga-Al-As laser) were employed. The parameters were 1.0 W in continuous-wave mode with an irradiation time of 30 s for the CO2 laser, 30 mJ in continuous-wave mode with an irradiation time of 60 s for the Er:YAG laser, and 1.0 W in continuous-wave mode with an irradiation time of 60 s for the Ga-Al-As laser. A non-irradiated group was used as a control. After laser irradiation, the dentinal surface of each sample was observed using SEM. Afterwards, all samples were immersed in methylene blue dye solution in order to evaluate the penetration of the dye solution and observe the change in dentinal permeability after laser irradiation. SEM observation showed that the control group had numerous exposed dentinal tubule orifices, whereas these orifices were closed in the laser-irradiated groups. There was consistent dye penetration into the pulp chamber in the control group, whereas no dye penetration was evident in the laser-irradiated groups. Therefore, laser appears to be a promising treatment for reducing permeation through exposed dentinal tubules

Stimulatory Effects of CO2 Laser, Er:YAG Laser and Ga-Al-As Laser on Exposed Dentinal Tubule Orifices

We investigated the effects of lasers irradiation on the exposed dentinal tubule. Human tooth specimens with exposed dentinal tubule orifices were used. Three types of lasers (CO2 laser, Er:YAG laser and Ga-Al-As laser) were employed. The parameters were 1.0 W in continuous-wave mode with an irradiation time of 30 s for the CO2 laser, 30 mJ in continuous-wave mode with an irradiation time of 60 s for the Er:YAG laser, and 1.0 W in continuous-wave mode with an irradiation time of 60 s for the Ga-Al-As laser. A non-irradiated group was used as a control. After laser irradiation, the dentinal surface of each sample was observed using SEM. Afterwards, all samples were immersed in methylene blue dye solution in order to evaluate the penetration of the dye solution and observe the change in dentinal permeability after laser irradiation. SEM observation showed that the control group had numerous exposed dentinal tubule orifices, whereas these orifices were closed in the laser-irradiated groups. There was consistent dye penetration into the pulp chamber in the control group, whereas no dye penetration was evident in the laser-irradiated groups. Therefore, laser appears to be a promising treatment for reducing permeation through exposed dentinal tubules