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PurposeTreatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment.MethodsPatients with de novo DLS, aged ≥ 65 years, who had LBP with visual analog scale (VAS) of ≥ 50 for ≥ 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated.ResultsOne hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 ± 32.4 and 43.9 ± 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs.ConclusionBone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.

Purpose Vertebral endplate lesions (EPLs) caused by severe disk degeneration are associated with low back pain. However, its pathophysiology remains unclear. In this study, we aimed to develop a vertebral EPL rat model mimicking severe intervertebral disk (IVD) degeneration by injecting monosodium iodoacetate (MIA) into the IVDs and evaluating it by assessing pain-related behavior, micro-computed tomography (CT) findings, and histological changes. Methods MIA was injected into the L4-5 and L5-6 IVDs of Sprague–Dawley rats. Their behavior was examined by measuring the total distance traveled and the total number of rearing in an open square arena. Bone alterations and volume around the vertebral endplate were assessed using micro-CT. Safranin-O staining, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining were performed for histological assessment. Results The total distance and number of rearing times in the open field were significantly reduced in a time-dependent manner. Micro-CT revealed intervertebral osteophytes and irregularities in the endplates at 12 weeks. The bone volume/tissue volume (BV/TV) around the endplates significantly increased from 6 weeks onward. Safranin-O staining revealed severe degeneration of IVDs and endplate disorders in a dose- and time-dependent manner. Calcitonin gene-related peptide-positive nerve fibers significantly increased from 6 weeks onward. However, the number of osteoclasts decreased over time. Conclusion Our rat EPL model showed progressive morphological vertebral endplate changes in a time- and concentration-dependent manner, similar to the degenerative changes in human IVDs. This model can be used as an animal model of severe IVD degeneration to better understand the pathophysiology of EPL.

PurposeVertebral endplate lesion (EPL) caused by severe disc degeneration is associated with low back pain. However, there is no suitable animal model to elucidate the pathophysiology of EPL. This study aimed to develop a rat model of EPL and evaluate rat behavior and imaging and histological findings.MethodsThe L4-5 intervertebral discs of Sprague–Dawley rats were transperitoneally removed, except for the outer annulus fibrosus and cartilage endplate, in the EPL group. The L4-5 discs were not removed and simply exposed in the sham group. Changes around the vertebral endplate on magnetic resonance imaging (MRI) and computed tomography (CT) were evaluated. Additionally, pain-related behavioral and histological assessments were performed.ResultsIn the EPL group, a low-signal area around the vertebral endplate was observed on T1-weighted and T2-weighted fat-saturated MRI at 8 weeks or later after surgery. In the same group, CT showed osteosclerosis around the vertebral endplate at 12 weeks after surgery. The sham group did not show abnormal imaging features on the MRI and CT. Behavioral evaluation showed that the EPL group had a significantly longer grooming time than the sham group. Conversely, the 12-week postoperative locomotion time and the 1- and 12-week postoperative standing times were significantly shorter in the EPL group than in the sham group. Histological evaluation showed a high degree of vertebral endplate degeneration and an increased number of osteoclasts and proportion of nerve fibers expressing calcitonin gene-related peptide in the EPL group compared to those in the sham group.ConclusionOur rat EPL model showed pain-related behavioral patterns and an increased expression of pain-related neuropeptide. This model could contribute to the study of the pathophysiology of EPL and will help in the treatment of low back pain in the future.

A major problem in hepatitis C virus (HCV) immunotherapy or vaccine design is the extreme variability of the virus. We identified human monoclonal antibodies (mAbs) that neutralize genetically diverse HCV isolates and protect against heterologous HCV quasispecies challenge in a human liver–chimeric mouse model. The results provide evidence that broadly neutralizing antibodies to HCV protect against heterologous viral infection and suggest that a prophylactic vaccine against HCV may be achievable.

Many aspects of the hepatitis C virus (HCV) life cycle have not been reproduced in cell culture, which has slowed research progress on this important human pathogen. Here, we describe a full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc). Replication of HCVcc was robust, producing nearly 105infectious units per milliliter within 48 hours. Virus particles were filterable and neutralized with a monoclonal antibody against the viral glycoprotein E2. Viral entry was dependent on cellular expression of a putative HCV receptor, CD81. HCVcc replication was inhibited by interferon-α and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals.

Study Design: Cross-sectional study.Purpose: We aimed to quantitatively assess bone marrow edema (BME) on magnetic resonance imaging (MRI) for patients with degenerative lumbar diseases.Overview of Literature: BME adjacent to a sclerotic endplate of the lumbar spine, detected using T2-weighted fat-saturated MRI, is closely associated with low back pain in patients with degenerative lumbar diseases. However, currently, there no quantitative evaluation methods for BME adjacent to the vertebral endplate.Methods: Patients with degenerative lumbar diseases, whose MRIs detected BME, were enrolled. On a T2-weighted fat-saturated MRI, BME appeared as a high-intensity region adjacent to the vertebral endplate. We calculated the contrast ratios (CRs) of BME and normal bone marrow using the signal intensities of BME, normal bone marrow, and the spinal cord. On computed tomography, we calculated Hounsfield unit (HU) values in the same area as BME, the sclerotic endplate, and normal bone marrow to assess bone density.Results: There were 16 men and 14 women, with an average age of 73.5 years. The mean CRs of BME and normal bone marrow were −0.015±0.056 and −0.407±0.023, respectively. BME’s CR was significantly higher than that of normal bone marrow (p<0.01). The HU values in the same area as BME, the sclerotic endplate, and normal bone marrow were 251.9±24.6, 828.3±35.6, and 98.1±9.3, respectively; these values were significantly different from each other (p<0.01).Conclusions: The CR on MRI is a useful quantitative assessment tool for BME in patients with degenerative lumbar diseases.

Intervertebral bridging ossification (IBO) occasionally occurs after balloon kyphoplasty (BKP) for osteoporotic vertebral fractures (OVFs), contributing to stabilization. However, the predisposing factors remain unclear. This study aimed to identify preoperative factors associated with IBO formation. This was a retrospective cohort study of patients who underwent BKP for OVFs. Radiological evaluations included the location of the fractured vertebra, number of preexisting vertebral fractures, endplate damage, intervertebral disc injury, presence of diffuse idiopathic skeletal hyperostosis, lateral wedge angle and regional kyphosis angle, and were assessed using radiography, computed tomography and magnetic resonance imaging (MRI). Clinical outcomes were evaluated via the visual analogue scale (VAS) and Oswestry Disability Index (ODI) preoperatively and at 1 month and 1 year postoperatively. Patients with IBO showed higher rates of thoracolumbar junction fractures (T11-L1) ( < 0.001), more preexisting vertebral fractures ( < 0.001), proximal endplate injury ( < 0.001), increased T2-weighted signal intensity of the adjacent intervertebral disc ( = 0.015) and larger lateral wedge angles in supine ( = 0.008) and sitting positions ( = 0.001). At 1 month, VAS scores were higher in the IBO group (4.2 ± 1.8 vs. 2.6 ± 2.0, = 0.001). Multiple regression analysis revealed preexisting vertebral fractures ( < 0.001) and proximal endplate injury ( = 0.002) as independent predictors of IBO formation. VAS scores at 1 month postoperatively were worse in the IBO group ( = 0.001), but no significant differences were observed at 1 year. Preexisting vertebral fractures and proximal endplate injury are key predictors of IBO formation after BKP. Although associated with higher short-term pain, IBO appears to contribute to long-term stabilization and pain relief, providing insights into postoperative outcomes and treatment strategies.

In this study, we review the agarose native gel electrophoresis that separates proteins and macromolecular complexes in their native state and transfer of the separated proteins from the agarose gel to membranes by contact blotting which retains the native state of these structures. Green fluorescent protein showed functional state both on agarose gel and blotted membrane. Based on the combined procedures, we discovered conformation-specific monoclonal antibodies against PLXDC2 and SARS-CoV-2 spike protein.

Numerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, very few molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human cord blood HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2 -GFP), we showed that Plxdc2 -GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2 -GFP + CD150 + cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2 + HSCs have higher long-term multilineage reconstitution ability compared with PLXDC2 - HSCs in a xenograft model. This study identifies PLXDC2 as a highly relevant molecule in HSC identification. PLXDC2 marks hematopoietic stem cells in mouse and human cord blood, enabling reliable identification with reporter mice and an antibody, and serving as a tool for imaging and transplantation studies.

We searched for cell-surface-associated proteins overexpressed on B cell chronic lymphocytic leukemia (CLL) to use as therapeutic antibody targets. Antibodies binding the immunosuppressive molecule CD200 were identified by cell panning of an antibody phage display library derived from rabbits immunized with primary CLL cells. B cells from 87 CLL patients exhibited 1.6- to 5.4-fold cellsurface up-regulation of CD200 relative to normal B cells. An effect of increased CD200 expression by CLL cells on the immune system was evaluated in mixed lymphocyte reactions. Addition of primary CLL but not normal B cells to macrophages and T cells down-regulated the Th1 response, as seen by a 50-95% reduction in secreted IL-2 and IFN-γ. Antibodies to CD200 prevented downregulation of the Th1 response in most B cell CLL samples evaluated, indicating abrogation of the CD200/CD200R interaction can be sufficient to restore the Th1 response. A disease-progression-associated shift of the immune response from Th1 to Th2 has been observed in numerous cancers. Because this cytokine shift is also believed to promote the induction of regulatory T cells, reverting the immune response to Th1 through direct targeting of the cancer cells may provide therapeutic benefits in CLL by encouraging a cytotoxic T cell response.