ヒト肝細胞癌においてherpesvirus entry mediatorの発現がもたらす影響

BACKGROUND: Herpes virus entry mediator (HVEM), also known as tumour necrosis factor receptor (TNFR) superfamily 14, regulates a variety of physiological and pathological responses in both innate and acquired immunity. Although HVEM is also suggested to be a critical regulator in tumours, actual roles in human cancer are largely unknown. This study aimed to clarify clinical importance of HVEM in human hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We studied HVEM expression in 150 HCC patients to explore its clinical relevance, and we examined tumour infiltrating T cells and local immune status of them. RESULTS: HVEM was expressed in HCC cells, while no or only limited expression was observed in normal tissues in the liver. Tumour HVEM expression was significantly correlated with age, serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level, vascular invasion and tumour node metastasis (TNM) stage. Furthermore, tumour HVEM expression significantly correlated with postoperative recurrence and survival. Importantly, multivariate analysis indicated that the HVEM status had an independent prognostic value. Furthermore, HVEM status was inversely correlated with tumour-infiltrating CD4(+), CD8(+) and CD45RO(+) lymphocytes. In addition, it was also associated with reduced expression of perforin, granzyme B and interferon-γ (IFN-γ). Taken together, tumour-expressing HVEM plays a functionally important role in HCC. CONCLUSION: Tumour-expressing HVEM plays a critical role in human HCC, possibly through regulating immune evasion. Therefore, targeting HVEM may be a novel promising therapeutic strategy for HCC.博士（医学）・乙第1359号・平成27年5月28日Copyright © 2014 Elsevier Ltd

The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases

Varner L.R., Chaya T., Maeda Y., et al. The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases. iScience 27, 109380 (2024); https://doi.org/10.1016/j.isci.2024.109380.Primary and secondary cone photoreceptor death in retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), leads to severe visual impairment and blindness. Although the cone photoreceptor protection in retinal degenerative diseases is crucial for maintaining vision, the underlying molecular mechanisms are unclear. Here, we found that the deubiquitinase Otud7b/Cezanne is predominantly expressed in photoreceptor cells in the retina. We analyzed Otud7b−/− mice, which were subjected to light-induced damage, a dry AMD model, or were mated with an RP mouse model, and observed increased cone photoreceptor degeneration. Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-κB activity. Furthermore, inhibition of NF-κB attenuated cone photoreceptor degeneration in the light-exposed Otud7b−/− retina and stress-induced neuronal cell death resulting from Otud7b deficiency. Together, our findings suggest that Otud7b protects cone photoreceptors in retinal degenerative diseases by modulating NF-κB activity

Preoperative and Postoperative Pulmonary Function in Elderly Patients with Thoracolumbar Kyphoscoliosis

Study DesignCase series.PurposeThe objective of this study was to investigate the change in pulmonary function in adult patients with a spinal deformity who underwent spinal corrective surgery.Overview of LiteratureDegenerative lumbar and/or thoraco-lumbar deformities are is often prominent in adult spinal deformity cases, whereas a thoracic deformity involving the chest wall is inconspicuous. A lumbar spine deformity could affect the pulmonary function; however, few reports have investigated pulmonary function in adult patients with a spinal deformity.MethodsThis study included 14 adult patients with a spinal deformity who underwent posterior corrective fusion (3 males, 11 females; mean age, 67.4 years). We measured percent vital capacity (%VC) and percent forced expiratory volume in 1 second (%FEV1) before surgery and six months after surgery. We investigated the change in pulmonary function after corrective surgery and the correlation between radiographic parameters and pulmonary function.ResultsMean preoperative %VC and %FEV1 values were 99.9% and 79.3%, respectively. Two cases were diagnosed with restrictive impairment, and two cases were diagnosed with obstructive impairment before surgery. %VC improved in the restrictive impairment cases six months after surgery. However, %FEV1 did not improve significantly after surgery in the obstructive impairment cases.ConclusionsRestrictive impairment was improved in adult patients with a spinal deformity by corrective spinal surgery. However, spinal surgery did not improve obstructive impairment

Serial MRI Features of Canine GM1 Gangliosidosis: A Possible Imaging Biomarker for Diagnosis and Progression of the Disease

GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies

Hypoglossal Nerve Palsy as a Complication of an Anterior Approach for Cervical Spine Surgery

A recurrent laryngeal nerve injury is known as a complication referring to an anterior cervical spine surgery. However, hypoglossal nerve injury is not well known yet. Herein we report a rare case of a 39-years-old male with a hypoglossal nerve injury after C3/4 osteophyte resection with Smith-Robinson approach. In this case there appeared difficulties of articulation and tongue movement with deviation of the tongue to the left side after the surgery and we diagnosed a hypoglossal nerve injury due to retraction against the nerve during the operation. During the operative approach to the upper cervical spine we had to retract the internal carotid artery and the soft tissue to reach the vertebrae. This retract was the cause of the hypoglossal nerve injury. A gently traction and intermittent release is important to avoid a hypoglossal nerve damage

Novel Measurement Technique for the Sagittal Vertical Axis and Its Clinical Application in Adult Spinal Deformity

Study DesignProspective physical measurement of the sagittal vertical axis (SVA).PurposeTo evaluate a simple method for measuring SVA by analyzing its relationship with radiographic measurements and clinical appearance.Overview of LiteratureNo studies have examined physical measurements using the cranial center of gravity (CCG) in a relaxed standing position.MethodsThe physical measurement of the horizontal distance between CCG and spina iliaca posterior superior (CCG-SIPS) was measured using a straight ruler in 252 healthy volunteers and 56 patients with adult spinal deformity. Health-related quality of life (HRQOL) was evaluated using the Oswestry disability index (ODI), and clinical symptoms were assessed according to standing status and the presence of gastroesophageal reflux disease (GERD).ResultsCCG-SIPS increased with age in the volunteer group and strongly correlated with radiographic SVA in the patient group (r=0.984). Differences increased between CCG-SIPS in patients in the relaxed position and radiographic SVA with an increase in sagittal malalignment (r=0.692, p120 mm) was significantly larger in the patient group than in the group with low sagittal malalignment (59.9±18.8 vs. 45.1±17.0; p=0.004); these patients (CCG-SIPS>120 mm) needed crutches or walkers for standing. The patient group with GERD had significantly larger sagittal malalignment than the group without GERD (160.3 mm vs. 81.0 mm).ConclusionsThe CCG-SIPS correlated with age and strongly reflected radiographic SVA and HRQOL in the patients. Moreover, it reflects a relaxed posture without a backward shift in the radiographic position even in patients with severe sagittal malalignment. The critical limit of CCG-SIPS can be relevant to clinical appearance, including standing assistance (>120 mm) and the existence of GERD (>150 mm). Thus, it will be a useful predictor of true SVA in clinical practice before radiographic evaluation

Low magnetic field promotes recombinant human BMP-2-induced bone formation and influences orientation of trabeculae and bone marrow-derived stromal cells

Effects of high magnetic fields [MFs, ≥ 1 T (T)] on osteoblastic differentiation and the orientation of cells or matrix proteins have been reported. However, the effect of low MFs (< 1 T) on the orientation of bone formation is not well known. This study was performed to verify the effects of low MFs on osteoblastic differentiation, bone formation, and orientation of both cells and newly formed bone. An apparatus was prepared with two magnets (190 mT) aligned in parallel to generate a parallel MF. In vitro, bone marrow-derived stromal cells of rats were used to assess the effects of low MFs on cell orientation, osteoblastic differentiation, and mineralization. A bone morphogenetic protein (BMP)-2-induced ectopic bone model was used to elucidate the effect of low MFs on microstructural indices, trabecula orientation, and the apatite c-axis orientation of newly formed bone. Low MFs resulted in an increased ratio of cells oriented perpendicular to the direction of the MF and promoted osteoblastic differentiation in vitro. Moreover, in vivo analysis demonstrated that low MFs promoted bone formation and changed the orientation of trabeculae and apatite crystal in a direction perpendicular to the MF. These changes led to an increase in the mechanical strength of rhBMP-2-induced bone. These results suggest that the application of low MFs has potential to facilitate the regeneration of bone with sufficient mechanical strength by controlling the orientation of newly formed bone.Okada R., Yamato K., Kawakami M., et al. Low magnetic field promotes recombinant human BMP-2-induced bone formation and influences orientation of trabeculae and bone marrow-derived stromal cells. Bone Reports, 14, 100757. https://doi.org/10.1016/j.bonr.2021.100757

Relationship between Spinal Hemangioblastoma Location and Age

Study DesignRetrospective case series.PurposeTo investigate the relationship between tumor location and clinical characteristics.Overview of LiteratureHemangioblastoma is a rare disease that develops in the central nervous system. Magnetic resonance imaging (MRI) is useful to evaluate hemangioblastomas. Hemangioblastoma's location is designated as intramedullary, intramedullary+extramedullary, or extramedullary by MRI.MethodsWe analyzed 11 patients who underwent surgery for spinal hemangioblastoma. Using T1 contrast axial MRI data, the cases were divided into three groups (intramedullary, intramedullary+extramedullary, and extramedullary). Patient demographics, MRI findings, and preoperative neurological status were analyzed and compared for each group.ResultsThe average age of patients with intramedullary, intramedullary+extramedullary, and extramedullary hemangioblastoma was 34.0, 64.4, and 67.5 years, respectively. Patients in the intramedullary hemangioblastoma group were younger than the other groups. Extramedullary cases had a smaller syrinx compared to the other groups.ConclusionsAge may play an important role in the hemangioblastoma tumor location and the subsequent diagnosis by an MRI

Response to: Hypoglossal Nerve Unjury after Cervical Spine Surgery

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Difference in Spinal Sagittal Alignment and Health-Related Quality of Life between Males and Females with Cervical Deformity

Study DesignLarge cohort study.PurposeTo clarify spinal sagittal alignment and health-related quality of life (HRQOL) according to sex in volunteers aged >50 years with cervical deformity (CD).Overview of LiteratureAdult spinal deformities, especially those associated with lumbosacral lesions, are more frequent in females; however, CD is observed to a greater extent in males.MethodsWe divided 656 volunteers (263 males, 393 females; age, 50–89 years [mean, 73 years]) as follows: males with CD (CDM; 82 patients); males without CD (NCDM, 181); females with CD (CDF, 36); and females without CD (NCDF, 357). CD was defined as C2–7 sagittal vertical axis (SVA) ≥40 mm. We measured pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI−LL), thoracic kyphosis, T1 slope, cervical lordosis, C7 SVA, and C2–7 SVA. HRQOL was evaluated using EuroQOL five dimensions questionnaire (EQ-5D).ResultsIn CDM, NCDM, CDF, and NCDF groups, the respective parameters were as follows: PT: 15°, 14°, 26°, and 21°; PI−LL: 7°, 5°, 16°, and 10°; C2–7 SVA: 49, 24, 46, and 20 mm; C7 SVA: 61, 40, 75, and 47 mm; and EQ-5D: 0.82, 0.88, 0.78, and 0.81. PT and PI−LL were significantly greater in the CDF group than in the NCDF group (p<0.05) but were not significantly different between CDM and NCDM groups. The CDF group already showed deterioration of spinopelvic alignment, although it was maintained in the CDM group. EQ-5D in showed significantly greater deterioration the CDM group than in the NCDM group; deterioration of lumbopelvic parameters had less influence in males (p<0.05).ConclusionsSagittal spinal deformity may have different mechanisms in males and females. The deterioration of spinal sagittal alignment in males may originate from the cervical spine, and CD may be associated with HRQOL