Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.

PURPOSE: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. METHODS: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. RESULTS: Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). CONCLUSIONS: From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.

Mesenchymal cell TRPM7 expression is required for bone formation via the regulation of chondrogenesis.

Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca2+ and Mg2+. Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation. Prx1-Cre-dependent Trpm7 mesenchymal-deleted mice were generated to examine the role of TRPM7 in bone development. We found that Prx1-Cre;Trpm7fl/fl mice had shortened bones and impaired trabecular bone formation. Trabecular bone parameters, such as the bone volume (BV/TV), and trabecular number (Tb.N), were decreased in Prx1-Cre;Trpm7fl/fl mice. The cortical bone parameters of cortical bone area (Ct.Ar) and cortical bone thickness (Ct.Th) were also down-regulated in these mice. The bone formation rate in Prx1-Cre;Trpm7fl/fl mice was unchanged, but the hypertrophic area and cell size of the zone were smaller, and the expression of Col2a1, Col10a1 and Mmp13 was downregulated compared with control mice. These findings suggest impaired chondrogenesis in Prx1-Cre;Trpm7fl/fl mice compared to control mice. The receptor activator of nuclear factor-kappa B ligand (RANKL) expression was increased, and RANKL-positive cells and osteoclasts were markedly accumulated in the boundary region between the growth plate and trabecular bone. In contrast, TRPM7 KR mice, which are kinase-dead mutants in which the TRPM7 ion channel function has not been altered, showed no marked differences in trabecular or cortical bone parameters compared to wild-type mice. These findings suggest that TRPM7 is critical as a cation channel rather than as a kinase in bone development via the regulation of chondrogenesis.

Endovascular Treatment of Tandem Atherosclerotic Cervical Internal Carotid Artery Occlusion in the Setting of Acute Ischemic Stroke.

BACKGROUND: Among tandem occlusions, atherosclerotic cervical internal carotid artery occlusion (ACICAO) can be technically challenging and associated with its unique complications. We evaluated our experience with endovascular treatment (EVT) of ACICAO in the setting of acute ischemic stroke. METHODS: In total, 154 consecutive patients who underwent EVT for acute anterior circulation stroke at our institute were retrospectively reviewed. Patients with tandem ACICAO were analyzed in this study. Procedures, recanalization rates, complications, and prognoses were evaluated. RESULTS: Ten patients (6%) of all 154 patients had ACICAO. In nine (90%) of the 10 patients, cervical lesions were successfully crossed and intervened upon. Four patients underwent stenting and five underwent angioplasty alone, followed by intracranial procedure. Eight patients (80%) achieved successful recanalization following mechanical thrombectomy for intracranial occlusion. However, one patient had massive subarachnoid hemorrhage during the procedure and another patient developed massive intracranial hemorrhage after EVT, both after stenting. Four of the five patients who initially underwent angioplasty alone subsequently underwent staged endarterectomy or stenting for residual stenosis on or after the next day. The single patient in whom the cervical lesion could not be crossed and another with reocclusion after EVT underwent a rescue bypass procedure due to persistent ischemic symptoms. After 90 days, four patients (40%) were functionally independent (modified Rankin scale score 0-2). CONCLUSIONS: Our experience suggests that EVT for ACICAO is technically feasible; however, it involves the potential risk of several significant complications. To avoid serious hemorrhagic complications, cervical lesions may be better treated with angioplasty alone first.

Ligand-Dissociation-Type N,N-Dimethylaminopyrene Probes for In-Situ Site-Specific Protein Labeling.

To develop practical methods for in-situ labeling of target proteins and to analyze their binding modes with bioactive ligands, 6-N,N-dimethylaminopyrene-N-acyl-N-alkylsulfonamide-4,8-diazacyclononyne (dmpy-NASA-DACN) tags were synthesized. Strain-promoted azide-alkyne cyclization with azide-conjugated ligands (biotin and sulfonamide) gave ligand-dissociation-type dmpy probes. With these probes, specific labeling of avidin and human carboxylase 1 (hCA1) proceeded even in the presence of cell lysate proteins in ca. 10% RIPA buffer. Affinity purification, in-gel tryptic digestion on polystyrene gel, and MALDI MS analysis established the dmpy-labeled positions of target proteins. Molecular modeling studies also supported why the dmpy-labeling reactions proceeded site-specifically near ligand-binding sites on the target proteins. Our findings might contribute to the development of chemical probes that specifically label various biomacromolecules in cells.

Odontoblast death drives cell-rich zone-derived dental tissue regeneration.

Severe dental tissue damage induces odontoblast death, after which dental pulp stem and progenitor cells (DPSCs) differentiate into odontoblast-like cells, contributing to reparative dentin. However, the damage-induced mechanism that triggers this regeneration process is still not clear. We aimed to understand the effect of odontoblast death without hard tissue damage on dental regeneration. Herein, using a Cre/LoxP-based strategy, we demonstrated that cell-rich zone (CZ)-localizing Nestin-GFP-positive and Nestin-GFP-negative cells proliferate and differentiate into odontoblast-like cells in response to odontoblast depletion. The regenerated odontoblast-like cells played a role in reparative dentin formation. RNA-sequencing analysis revealed that the expression of odontoblast differentiation- and activation-related genes was upregulated in the pulp in response to odontoblast depletion even without damage to dental tissue. In this regenerative process, the expression of type I parathyroid hormone receptor (PTH1R) increased in the odontoblast-depleted pulp, thereby boosting dentin formation. The levels of PTH1R and its downstream mediator, i.e., phosphorylated cyclic AMP response element-binding protein (Ser133) increased in the physically damaged pulp. Collectively, odontoblast death triggered the PTH1R cascade, which may represent a therapeutic target for inducing CZ-mediated dental regeneration.

Iatrogenic intracranial vessel dissection during mechanical thrombectomy rescued by emergent stenting: 2 case reports.

Intracranial vessel dissection is a procedural complication associated with endovascular treatment. However, there have been few reports on its potential causes and management during mechanical thrombectomy. In approximately 250 cases of mechanical thrombectomy over the past 5 years at our institution, iatrogenic intracranial dissection occurred in 2 patients (0.8%). In this report, we described these 2 cases that were rescued through emergent stenting. Mechanical thrombectomy, using both a stent retriever and an aspiration catheter, was performed for acute middle cerebral artery M2 occlusion in Patient 1 (a 69-year-old man) and for distal M1 occlusion in Patient 2 (an 83-year-old woman). In both cases, recanalization was achieved with the procedure, but irregular stenosis developed at the initially nonoccluded, but mildly arteriosclerotic, M1, after recanalization. During the thrombectomy procedure, the aspiration catheter sifted up to the arteriosclerotic M1. In both cases, the lesions were considered vessel dissection, due to a shift of the aspiration catheter tip into the arteriosclerotic vessel wall. Repeated percutaneous angiography with antithrombotic therapy failed to improve the lesions and to maintain the antegrade blood flow. Finally, lesions in each patient were successfully rescued through the use of emergent stenting. A drug-eluting stent for coronary use was deployed in Patient 1, and an Enterprise stent was applied in Patient 2. Inadvertent shift of the aspiration catheter into arteriosclerotic vessels can cause a serious intracranial vessel dissection. When performing mechanical thrombectomy, intracranial stents need to be available as rescue treatment devices to manage refractory iatrogenic intracranial vessel dissection.

RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp.

Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed. High OPG expression was expected to have a negative regulatory effect on odontoclastogenesis; however, odontoclasts were not detected in the dental pulp of OPG-deficient (KO) mice. In contrast, damage induced odontoclast-like cells were seen in wild-type pulp tissues, with their number significantly increased in OPG-KO mice. Relative ratio of RANKL/OPG in the damaged pulp was significantly higher than in undamaged control pulp. Pulp damages enhanced hypoxia inducible factor-1α and -2α, reported to increase RANKL or decrease OPG. These results reveal that the relative ratio of RANKL/OPG is significant to pulpal odontoclastogenesis, and that OPG expression is not required for maintenance of pulp homeostasis, but protects pulp from odontoclastogenesis caused by damages.

Symptomatic Intracranial Artery Stenosis Due to an Unknown Embolus Following Cardiac Surgery: A Case Report.

Intracranial artery occlusion due to a foreign body is a complication associated with cardiac surgery that is treated by various techniques. However, little is known about appropriate strategies for symptomatic intracranial artery stenosis due to an unknown embolic source. We reported a case of middle cerebral artery (MCA) stenosis after mitral valve repair (MVR) for infective endocarditis (IE). An 80-year-old man presented with right hemiplegia. MR angiography findings were normal, and diffusion-weighted imaging revealed subtle ischemic change in the left MCA territory. The patient was diagnosed with cardioembolic stroke owing to IE and performed MVR. Four days later, he suddenly presented with consciousness disorder and left hemiplegia. Computed tomography (CT) confirmed a very low-density area within the right MCA. MR angiography revealed right MCA stenosis, which corresponded to the low-density area on CT images. Diffusion-weighted imaging revealed new ischemic change in the right MCA territory. Angiography confirmed an irregular stenosis at the right M2 with antegrade blood flow, and the hemiplegia resolved during angiography. Conservative therapy was performed; however, the resting 123 I-IMP-single photon emission CT revealed moderate perfusion defect in the right MCA territory, and transient left hemiplegia appeared every few days. Therefore, 19 days after the initial transient ischemic attack, the patient was performed superficial temporal artery-MCA anastomosis, and the patient responded with a good clinical course without recurrence of the ischemic symptoms. This strategy may be a safe and effective treatment for symptomatic intracranial artery stenosis due to an unknown embolic source.

N,N-Dimethylaminopyrene as a fluorescent affinity mass tag for ligand-binding mode analysis.

Elucidation of the binding mode of protein-ligand interactions provides insights for the design of new pharmacological tools and drug leads. Specific labeling of target proteins with chemical probes, in which the ligands are conjugated with reacting and detecting groups, can establish the binding positions of ligands. Label-assisted laser desorption/ionization mass spectrometry (LA-LDI MS) is a promising detection method to selectively detect labeled molecules. However, previous LDI MS tags, such as nitrogen-substituted pyrenes, had problems with low sensitivity and stability. Here we show 6-N,N-dimethylaminopyrene (dmpy) as a versatile mass tag, which was detected at an amount of 0.1 fmol by LA-LDI MS and applicable for MS/MS analysis. By using ligand-dissociation-type dmpy probes and affinity purification with a polystyrene gel, we demonstrated that dmpy-labeled peptides were predominantly detected by MALDI MS. Our dmpy-probe-labeling method might be highly useful for determining the target biomacromolecules of various ligands and their binding sites.

Impact of introducing endovascular treatment on acute ischemic stroke outcomes: A shift from an era of medical management to thrombectomy in Japan.

BACKGROUND: Endovascular treatment (EVT) has increasingly become the standard treatment of acute cerebral large vessel occlusion (LVO). We evaluated the impact of introducing EVT on LVO therapy in a single center where intravenous thrombolysis (IVT) had been the only recanalization therapy. MATERIALS AND METHODS: Between April 2013 and March 2017, 354 consecutive patients with LVO admitted to our institution were analyzed. We compared outcomes between two chronological groups before (Pre-EVT group) and after (Post-EVT group) introducing EVT in April 2015. We assessed prognostic factors for favorable outcomes (modified Rankin scale score ≤2 at 90 days). RESULTS: In the Pre-EVT group, all 140 patients were treated medically, including 30 patients (21%) undergoing IVT. In the Post-EVT group, 118 patients (55%) underwent EVT, and the remaining 96 patients treated medically, including six patients (3%) undergoing IVT. The proportion undergoing recanalization therapy with IVT or EVT significantly increased after introducing EVT (21% versus 58%, p < 0.001). The rate of patients achieving favorable outcomes also significantly increased (14% versus 31%, p < 0.001). In multivariate regression analysis, introducing EVT was an independent predictive factor after adjusting for age, stroke severity and extent, and time (p = 0.005). The arrival time in patients with helicopter transport was significantly shorter than that with ground ambulance for a distance of more than 10 km (p < 0.001). CONCLUSIONS: This study demonstrated that the introduction of EVT improved outcomes of acute LVO patients, increasing the opportunity to receive recanalization therapy. Further efforts to establish medical systems to provide EVT are required throughout the country.

Surgical Thromboendarterectomy for Free-Floating Thrombus Associated with Cervical Carotid Artery Dissection: A Case Report.

BACKGROUND: Free-floating thrombus (FFT) of the cervical carotid artery is a rare but critical condition leading to stroke. The most common underlying pathology is atherosclerotic plaque; nonatherosclerotic pathologies are much rarer. Here we report a case of FFT associated with cervical carotid artery dissection that was successfully treated by surgical thromboendarterectomy. METHODS: A 51-year-old man presented with headache, pain in the left neck, and amaurosis fugax. Magnetic resonance angiography revealed mild stenosis in the bifurcation of the left carotid artery. The stenotic lesion was considered as a possible dissection because of the normal appearance of the vessel 2 years ago and its clinical presentation. Oral aspirin was initiated with the diagnosis of transient ischemic attack. Two weeks later, ultrasound was planned for further examination, which demonstrated a massive FFT with intramural hematoma in the lesion. Because FFT was present despite taking aspirin, surgical thromboendarterectomy was performed to prevent further ischemic events. RESULTS: Intraoperative findings revealed that FFT was the thrombus protruding from the intramural hematoma caused by arterial dissection. After the whole dissected layer was removed, the residual lumen was reinforced by multiple tacking sutures to prevent recurrence of dissection. No further ischemic events and recurrence occurred during the 1-year of follow-up after the surgery. CONCLUSIONS: When managing patients with carotid artery dissection, the formation of FFT should be considered as a possible critical feature. Surgical thromboendarterectomy with intimal tacking sutures might be an option for the treatment, ensuring immediate, preventive effects against the risk of cerebral embolism.

[Surgical Results of Lumbar Degenerative Disease with Foot Drop].

Drop foot is associated with various diseases, such as peripheral nerve disease, lumbar degenerative disease, metabolic disease, and endocrine disease. Among lumbar degenerative diseases, lumbar disc herniation and lumbar canal stenosis are most commonly reported. We report the surgical outcomes of patients with drop foot caused by lumbar degenerative diseases. Between 2008 and 2018, we encountered 24 cases of drop foot in patients who underwent surgery of the lumbar lesion. The mean age was 69.5 years(49-88 years). Fourteen patients were male and ten were female. The mean time interval between the onset of drop foot and surgery was 51.5 days(from 7 days to 1 year). Drop foot, as a clinically significant muscle weakness, was defined at levels of manual muscle test(MMT)3 or lower. Responsible lesions for drop foot were canal stenosis at L4/5 in 8 cases, disc herniation at L4/5 in 10 cases, disc herniation at L5/S1 in 5 cases, and far-out syndrome in 1. One case involved drop foot bilaterally. Muscle weakness improved by surgery at levels of MMT 4 or greater in 16 cases(66.7%). Six cases of complete paresis or tibialis anterior muscle atrophy preoperatively resulted in no improvement;however, neuralgia was relieved in all. Twelve of 15 cases(80%)of lumbar disc herniation and 4 of 10 cases(40%)of lumbar canal stenosis resulted in improvement. Between disc herniation and canal stenosis, the surgical success rate was not statistically different. Age and the time interval between the onset and surgery were also not significant factors of the outcome. Surgical intervention seems to be beneficial even in cases of severe muscle weakness since pain relief can be expected, which leads to improvement in gait.

Parathyroid Hormone Shifts Cell Fate of a Leptin Receptor-Marked Stromal Population from Adipogenic to Osteoblastic Lineage.

Intermittent parathyroid hormone (iPTH) treatment induces bone anabolic effects that result in the recovery of osteoporotic bone loss. Human PTH is usually given to osteoporotic patients because it induces osteoblastogenesis. However, the mechanism by which PTH stimulates the expansion of stromal cell populations and their maturation toward the osteoblastic cell lineage has not be elucidated. Mouse genetic lineage tracing revealed that iPTH treatment induced osteoblastic differentiation of bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs), which carried the leptin receptor (LepR)-Cre. Although these findings suggested that part of the PTH-induced bone anabolic action is exerted because of osteoblastic commitment of MSPCs, little is known about the in vivo mechanistic details of these processes. Here, we showed that LepR+ MSPCs differentiated into type I collagen (Col1)+ mature osteoblasts in response to iPTH treatment. Along with osteoblastogenesis, the number of Col1+ mature osteoblasts increased around the bone surface, although most of them were characterized as quiescent cells. However, the number of LepR-Cre-marked lineage cells in a proliferative state also increased in the vicinity of bone tissue after iPTH treatment. The expression levels of SP7/osterix (Osx) and Col1, which are markers for osteoblasts, were also increased in the LepR+ MSPCs population in response to iPTH treatment. In contrast, the expression levels of Cebpb, Pparg, and Zfp467, which are adipocyte markers, decreased in this population. Consistent with these results, iPTH treatment inhibited 5-fluorouracil- or ovariectomy (OVX)-induced LepR+ MSPC-derived adipogenesis in BM and increased LepR+ MSPC-derived osteoblasts, even under the adipocyte-induced conditions. Treatment of OVX rats with iPTH significantly affected the osteoporotic bone tissue and expansion of the BM adipose tissue. These results indicated that iPTH treatment induced transient proliferation of the LepR+ MSPCs and skewed their lineage differentiation from adipocytes toward osteoblasts, resulting in an expanded, quiescent, and mature osteoblast population. © 2019 American Society for Bone and Mineral Research.

Beclin1 Modulates Bone Homeostasis by Regulating Osteoclast and Chondrocyte Differentiation.

Autophagy (ATG), an important cellular recycling process whereby macromolecules or organelles are encapsulated by autophagosome and degraded upon merging with lysosome, has recently been shown to play an essential role in bone biology. However, the involvement of ATG in bone and bone-related cells remains unclear. Here, we show that Beclin1, an ATG-related protein involved in ATG initiation, plays a pivotal role in osteoclasts. ATG was activated during osteoclast differentiation in vitro. Beclin1 was enhanced and required for osteoclast differentiation. Mechanistically, we found that TRAF6-mediated ubiquitination of Beclin1 at K117, but not ULK1-mediated phosphorylation, is required for RANKL-stimulated osteoclast differentiation. In vivo, mice lacking Beclin1 in CstK-expressing cells exhibited an increased cortical bone thickness caused by impaired osteoclasts' function. Interestingly, these mice also exhibited diminished trabecular bone mass, which was associated with a defect in cartilage formation and chondrocyte differentiation. Collectively, our study highlights the functional importance of ATG in osteoclasts and chondrocytes, and identifies ATG as a potential therapeutic target for managing bone-related diseases. © 2019 American Society for Bone and Mineral Research.

Effects of Attachment of Plastic Aligner in Closing of Diastema of Maxillary Dentition by Finite Element Method.

The aim of this study was to clarify the effect of attachment on tooth movement produced by a plastic aligner. Closing of a diastema, in which the maxillary right and left central incisors moved bodily, was simulated using a finite element method. Long-term orthodontic movements of the maxillary dentition were simulated by accumulating the initial displacement of teeth produced by elastic deformation of the periodontal ligament. The incisor tipped and rotated just after placement of the aligner irrespective of the attachment. After a sufficiently long time, the incisor was upright and moved bodily in the aligner with attachment, but the incisor remained tipped in the aligner without attachment. It was demonstrated that the attachment was effective for achieving bodily movement.

[Implementation of Penumbra-assisted Half-Stent Thrombectomy for Patients with Acute M2 Occlusion:Results of Initial Experiences].

The benefits of mechanical thrombectomy(MT)for acute M2 occlusion have remained unclear because of unavoidable device-related complications due to vascular morphological characteristics. We developed a Penumbra-assisted half-stent thrombectomy for achieving secure retrieval of thrombus with minimal damage to the small-caliber vessel. In total, 6 patients were treated with MT for acute M2 occlusion using this technique between November 2016 and May 2017, including 3 men and 3 women, mean age 74.8(51-98)years. The mean baseline National Institutes of Health Stroke Scale score was 17.5(6-32), and Alberta Stroke Program Early Computed Tomography Score-Diffusion-Weighted Imaging was 7.5(6-9). After navigation of the microcatheter through the thrombus in M2 supported by a Penumbra 4MAX as a distal access catheter, the stent retriever(SR)was partially deployed to cover the entire thrombus. The 4MAX was then advanced towards the caudal end of the thrombus, and the SR was pulled back into the 4MAX with simultaneous aspiration of the 4MAX. We used the Trevo XP3 in 5 patients and Revive SE in 1 patient. The mean procedure time from groin puncture to recanalization was 60(54-66)min. Successful recanalization(Thrombolysis in Cerebral Infarction score 2b or 3)was achieved in 5(83%)patients. There were no cases of symptomatic intracranial hemorrhage. Good outcome(modified Rankin Scale score 0 to 2)at 3 months was achieved in 3(50%)patients. Penumbra-assisted half-stent thrombectomy appears to be an effective alternative strategy in MT for acute M2 occlusion.

Specific protein-labeling and ligand-binding position analysis with amidopyrene probes as LDI MS tags.

To readily analyze the binding mode of protein-ligand interactions, we developed ligand-bound-type and ligand-dissociation-type probes having 6-amidopyrene (apy) as a detecting group. Matrix- and label-assisted laser desorption/ionization mass spectrometry (MALDI and LA-LDI MS) analyses and a covalent docking simulation using these probes precisely determined the binding position of the ligand biotin on the target protein avidin (RMSD = 0.786 and 0.332 Å). Our apy-probe-labeling method may be useful for determining the unknown ligand-binding sites of various target proteins.

[Two Cases of Bilateral Orbital Metastases of Breast Cancer].

Two cases of breast cancer with bilateral orbital metastases associated with intracranial metastases are presented. Case 1:A 61-year-old woman who was diagnosed with breast cancer 14 years earlier presented with rapid deterioration of visual acuity, eye pain, and limitation of left-sided extraocular motility. Magnetic resonance(MR)images showed an enhanced lesion in the left orbital apex, ethmoid sinus, and right middle fossa. The first gamma knife radiotherapy(35 Gy, 5 Fr)was performed successfully, but was followed by recurrence 18 months later in the right intraorbital, where newly formed iso-intensity masses in the extraconal compartment were found. The second gamma knife radiosurgery was performed for three masses(20 Gy). Case 2:A 35-year-old woman with breast cancer who was diagnosed 22 months earlier was treated for meningeal carcinomatosis by whole-brain radiation(30 Gy, 10 Fr)and intrathecal chemotherapy. Eight months later, swelling in both eyelids and limitation of extraocular motility developed rapidly. MR imaging revealed an infiltrating lesion in the cone with heterogenous signal that was encasing, but not infiltrating the optic nerves. The extraconal lesion extended into the soft tissue of the lower eye lid. She expired one week after diagnosis. With the increasing number of long-term survivors with breast cancer, intraorbital metastases may be found during the course of treatment for intracranial lesions. Understanding the unique clinical presentation and characteristic MR findings of this rare entity are emphasized.

Histone Demethylase Jmjd7 Negatively Regulates Differentiation of Osteoclast.

OBJECTIVE: To identify and verify the histone modifier during osteoclastogenesis. METHODS: Murine macrophage-like cell line, RAW 264.7 cells, or murine bone marrow macrophages (BMMs) were treated with a receptor activator of nuclear factor B ligand (RANKL) alone or RANKL with macrophage colony-stimulating factor (M-CSF), respectively, to induce differentiation of osteoclast. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen different arrays of histone demethylases. Chromatin immunoprecipitation (ChIP) assay was used to examine occupancy of jumonji domain containing 7 (Jmjd7) in the promoter regions of different osteoclast-related genes. Jmjd7 was knocked down using siRNA. Dentine slice assay was used to evaluate bone-resorptive functions. RESULTS: Among the screened histone demethylases, Jmjd7 was significantly downregulated during differentiation of osteoclast. The occupancy of Jmjd7 at the promoter regions of osteoclast-related genes was also decreased. Knockdown of Jmjd7 in RAW 264.7 cells and BMMs enhanced differentiation of osteoclast and increased the expression of osteoclast-related genes, such as c-fos, Dc-stamp, CtsK, Acp5, and Nfatc1. Bone resorptive functions of the cells were also increased. CONCLUSION: Our study shows that Jmjd7, a histone demethylase, functions as a negative regulator of osteoclastogenesis, and may be a therapeutic target of bone-related diseases.