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1.
BMC Musculoskelet Disord ; 25(1): 297, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627691

ABSTRACT

BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


Subject(s)
Foot Injuries , Fractures, Bone , Free Tissue Flaps , Hyperemia , Osteomyelitis , Soft Tissue Injuries , Humans , Leg , Retrospective Studies , Free Tissue Flaps/adverse effects , Hyperemia/complications , Lower Extremity/surgery , Fractures, Bone/surgery , Fractures, Bone/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Soft Tissue Injuries/surgery , Soft Tissue Injuries/complications , Osteomyelitis/surgery , Osteomyelitis/complications , Necrosis/etiology , Necrosis/surgery , Treatment Outcome
2.
JPRAS Open ; 38: 48-59, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37675275

ABSTRACT

Background: During free flap surgery, the surgeon sometimes encounters problems with anastomosis such as intractable arterial spasms or vessel size discrepancy in venous anastomoses. End-to-side (ETS) anastomosis has the advantages of limited chance of vessel spasm and easy handling by adjusting for vessel size discrepancy. We introduced the arterial and venous end-to-side anastomosis (AV-ETS) strategy, which is based on the ETS anastomosis to the main artery and accompanying veins, to avoid intraoperative anastomotic problems when creating a free flap. The aim of this study was to compare flap outcomes and intraoperative anastomotic problems before and after introduction of the AV-ETS strategy in extremity free flap surgery. Materials and methods: We retrospectively examined 72 consecutive extremity free flaps. Before introducing the AV-ETS strategy, we used the conventional strategy in which the recipient artery was selected according to the number of the remaining main artery and the anastomosis technique was flexibly changed, although the end-to-end (ETE) technique was used in most cases. Results: The conventional group had 18 flaps and the AV-ETS group had 54 flaps. The rate of flap survival did not differ between these groups, and there were no cases of flap failure after the introduction of the AV-ETS strategy. The AV-ETS group had significantly fewer flaps that required a change in preoperative planning for the recipient artery or anastomotic site of the artery. Conclusions: The AV-ETS strategy may facilitate reliable preoperative planning and the performance of stable free flap surgery without requiring a flexible response during surgery.

3.
BMC Musculoskelet Disord ; 24(1): 356, 2023 May 06.
Article in English | MEDLINE | ID: mdl-37149570

ABSTRACT

BACKGROUND: The bacterial source of surgical-site infections (SSIs) can have either endogenous and/or exogenous origins, and some studies have revealed that endogenous transmission is an important pathway for SSIs in orthopedic surgery. However, since the frequency of SSIs is low (0.5-4.7%), screening all surgery patients is labor-intensive and cost-prohibitive. The goal of this study was to better understand how to improve the efficacy of nasal culture screening in preventing SSIs. METHODS: Nasal cultures for 1616 operative patients over a 3-year period were evaluated for the presence of nasal bacterial microbiota and the species identity. We also investigated the medical factors that influence colonization and evaluated the ratio of agreement between nasal cultures and SSI-causing bacteria. RESULTS: In a survey of 1616 surgical cases, 1395 (86%) were normal microbiota (NM), 190 (12%) were MSSA carriers, and 31 (2%) were MRSA carriers. The risk factors for MRSA carriers were significantly higher than the NM group in patients with a history of hospitalization (13 [41.9%], p = 0.015), patients who had been admitted to a nursing facility (4 [12.9%], p = 0.005), and patients who were > 75 years of age (19 [61.3%], p = 0.021). The incidence of SSIs was significantly higher in the MSSA group (17/190 [8.4%]) than the NM group (10/1395 [0.7%], p = 0.00). The incidence of SSIs in the MRSA group (1/31 [3.2%]) tended to be higher than that in the NM group, but there was no statistically significant difference (p = 0.114). The concordance rate between causative bacteria of SSI and species present in nasal cultures was 53% (13/25 cases). CONCLUSIONS: The results of our study suggest screening patients with a history of past hospitalization, a history of admission in a long-term care facility, and older than 75 to reduce SSIs. TRIAL REGISTRATION: This study was approved by the institutional review board of the authors' affiliated institutions (the ethics committee of Sanmu Medical Center, 2016-02).


Subject(s)
Orthopedic Procedures , Staphylococcal Infections , Humans , Surgical Wound Infection/diagnosis , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Staphylococcal Infections/diagnosis , Orthopedic Procedures/adverse effects , Risk Factors , Anti-Bacterial Agents/therapeutic use
4.
Neuropathology ; 43(5): 413-420, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36942363

ABSTRACT

Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.


Subject(s)
Astrocytoma , Brain Neoplasms , Enchondromatosis , Glioma , Oligodendroglioma , Female , Humans , Young Adult , Adult , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Enchondromatosis/complications , Enchondromatosis/genetics , Enchondromatosis/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , In Situ Hybridization, Fluorescence , Isocitrate Dehydrogenase/genetics , Glioma/genetics , Astrocytoma/genetics , Astrocytoma/pathology , Mutation
6.
Surg Neurol Int ; 13: 421, 2022.
Article in English | MEDLINE | ID: mdl-36324944

ABSTRACT

Background: Surgical indications for fragility fracture of the pelvis (FFP) have been reconsidered recently, and the indications to perform surgery have increased. However, the optimal surgical method to obtain sufficiently strong fixation in elderly patients with minimal invasiveness is not yet clear. In this report, we present the case of a patient with FFP who was treated with a novel posterior within ring fixation technique using a combination of iliac screws and an implant that locks the original iliosacral (IS) screw in the sacrum. Case Description: A 90-year-old man was diagnosed with FFP (Rommens classification: Type IIc) and hospitalized for conservative treatment. However, 6 weeks after the injury, pain reappeared in his right buttock and computed tomography showed additional fractures of the right subpubic branch and right sacrum (Rommens classification: Type IVb). The fracture was considered to have progressed from being stable to unstable, and surgical treatment was planned. To obtain strong fixation with minimal invasion, we performed posterior fixation using E.Spine Tanit (Euros, France) compact posterior thoracolumbar instrumentation, an implant that combines an IS screw with a sacral anchoring system. The patient started walking unaided 2 weeks after the surgery, suggesting a good outcome of this surgical approach to FFP. Conclusion: We performed posterior fixation surgery for a patient with an unstable FFP that recurred and progressed after conservative treatment. We have achieved good results using a minimally invasive, strong, and within ring fixation technique.

7.
JPRAS Open ; 34: 189-198, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36393895

ABSTRACT

Purpose: The availability of reliable and suitably sized veins is limited for creating free flaps to treat severe trauma and infection, and it is important to manage vessel size discrepancy between the recipient and flap veins. We evaluated the clinical outcomes of free flaps with large-to-small venous end-to-side (ETS) anastomoses using the microscopic parachute end-to-side (MPETS) anastomosis in soft tissue defects in the extremities. This procedure comprises mainly a wide-slit venotomy and parachute procedure at the heel. Methods: We examined 24 free flaps in 23 patients given a large-to-small venous anastomosis using the MPETS technique. Patient demographics, details of vessel anastomoses, and flap outcomes and complications were obtained from medical records. Results: Two veins were anastomosed in six flaps. Thirty anastomosed veins were assessed, and 24 deep veins, all of which accompanied main arteries, were chosen as recipient veins. The mean diameters were 1.5 mm in the recipient veins and 2.7 mm in the flap veins, and the mean vessel size discrepancy was 1.8-fold (range 1.3-3.3 fold). Because of the presence of venous valves at the anastomotic site, trimming of venous cusps was performed in six veins. All flaps survived, though one venous thrombosis occurred because of pedicle kinking in a case with a short pedicle. Conclusions: The MPETS technique is simple, reliable, and useful for performing various types of venous anastomoses regardless of a vessel size discrepancy and the presence of a venous valve. This may be a good option for large-to-small venous anastomosis in free flaps.

8.
BMC Musculoskelet Disord ; 23(1): 821, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36042450

ABSTRACT

BACKGROUND: Although total wrist arthroplasty (TWA) has become a common treatment option for wrists with damage due to rheumatoid arthritis (RA), the optimal implant axial alignment for TWA has been inadequately studied. This study was performed to investigate the relationships between implant alignment and carpal rotational alignment and the wrist range of motion (ROM) following TWA. METHODS: This study included 18 patients who underwent TWA using a DARTS® Total Wrist System (Teijin Nakashima Medical, Okayama, Japan) for wrist RA. Pre- and 6-month postoperative computed tomography scans were performed, including the radial volar line (Rv), capitohamate axis (CH), and Rv-CH angle in axial scans. The wrist ROM was also measured. The relationship between the Rv-CH angle and ROM was examined. RESULTS: The mean Rv-CH angle showed significant wrist pronation from 73.0° to 83.4° postoperatively. We observed a significant positive correlation (0.58) between the postoperative Rv-CH angle and extension and a significant negative correlation (- 0.56) between the postoperative Rv-CH angle and flexion. CONCLUSIONS: Implantation of the DARTS® TWA prosthesis resulted in pronation of the carpal axial alignment, which was correlated with postoperative wrist extension. The volar cortex of the distal radius can be a novel reference axis for adequate implant placement.


Subject(s)
Arthritis, Rheumatoid , Arthroplasty, Replacement , Carpal Bones , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement/adverse effects , Humans , Range of Motion, Articular , Wrist/surgery , Wrist Joint/diagnostic imaging , Wrist Joint/surgery
9.
Front Neurol ; 13: 832569, 2022.
Article in English | MEDLINE | ID: mdl-35432160

ABSTRACT

Recent studies suggest that blood flow changes in the median nerve may help confirm a diagnosis of carpal tunnel syndrome (CTS). Herein, we examined the utility of superb microvascular imaging (SMI), a new ultrasonographic (US) technique for visualizing microvascular flow, for detecting blood flow differences between CTS patients and healthy controls. We performed a retrospective analysis of 28 hands with suspected CTS. Patients received both nerve conduction and US examinations. Ten healthy volunteers were enrolled as the control group. The nerve compression ratio and the blood flow signal area were quantified using color Doppler US (CDUS), power Doppler US (PDUS), and SMI. Correlation analyses between the blood flow signal area, the compound muscle action potential of the thenar muscle, and the nerve compression ratio were performed. As a result, the mean nerve compression ratio was found to be significantly higher in the CTS group. There were no differences in the blood flow signal area between the groups using CDUS, while PDUS and SMI showed higher blood flow signals in the CTS group. The blood flow signal area measured by SMI had stronger correlations with the compound muscle action potential amplitude and the nerve compression ratio than those for PDUS. The diagnostic utility of SMI was equivalent to PDUS, but superior to conventional CDUS. Nevertheless, the blood flow signal by SMI was more strongly correlated with the electrophysiological severity and compression ratio than for PDUS. Use of SMI in future studies may help clarify the underlying mechanisms of blood flow changes in CTS.

10.
Case Rep Orthop ; 2022: 5584397, 2022.
Article in English | MEDLINE | ID: mdl-35251727

ABSTRACT

With the advancement of cancer treatment and minimally invasive surgery, the indications for surgery for metastatic spinal tumors are expanding. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory skeletal disease characterized by calcification and ossification of ligaments and entheses. In Japan, the prevalence of DISH is increasing with its superaging society. The purpose of this article is to report a case of applying a novel screw technique for pathological fracture in a patient with DISH and spinal metastasis. An 80-year-old man with spinal metastasis presented with acute onset of severe back pain, and investigations revealed a fracture of a metastatic lesion in T10-T12 in the range of DISH. We performed posterior fixation with a percutaneous pedicle screw system using a penetrating endplate technique. The patient's back pain improved, and he was able to mobilize with minimal assistance and survived for 8 months with a good quality of life. Spinal fracture accompanied by DISH sometimes occurs with severe instability because of injury across 3-column injury and its long lever arm. Spinal instability neoplastic score indicates instability of pathological fractures of spinal metastases but needs to be evaluated carefully when DISH is present. The prevalence of DISH is increasing in the elderly, and penetrating endplate screws can be an effective option in posterior fusion surgery for patients with DISH and spinal metastases.

11.
Int Immunol ; 33(8): 423-434, 2021 07 23.
Article in English | MEDLINE | ID: mdl-34036345

ABSTRACT

Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammation with lymphoid infiltration and destruction of the salivary glands. Although many genome-wide association studies have revealed disease-associated risk alleles, the functions of the majority of these alleles are unclear. Here, we show previously unrecognized roles of GTF2I molecules by using two SS-associated single nucleotide polymorphisms (SNPs), rs73366469 and rs117026326 (GTF2I SNPs). We found that the risk alleles of GTF2I SNPs increased GTF2I expression and enhanced nuclear factor-kappa B (NF-κB) activation in human salivary gland cells via the NF-κB p65 subunit. Indeed, the knockdown of GTF2I suppressed inflammatory responses in mouse endothelial cells and in vivo. Conversely, the over-expression of GTF2I enhanced NF-κB reporter activity depending on its p65-binding N-terminal leucine zipper domain. GTF2I is highly expressed in the human salivary gland cells of SS patients expressing the risk alleles. Consistently, the risk alleles of GTF2I SNPs were strongly associated with activation of the IL-6 amplifier, which is hyperactivation machinery of the NF-κB pathway, and lymphoid infiltration in the salivary glands of SS patients. These results demonstrated that GTF2I expression in salivary glands is increased in the presence of the risk alleles of GTF2I SNPs, resulting in activation of the NF-κB pathway in salivary gland cells. They also suggest that GTF2I could be a new therapeutic target for SS.


Subject(s)
Inflammation/genetics , Polymorphism, Single Nucleotide/genetics , Salivary Glands/pathology , Sjogren's Syndrome/genetics , Transcription Factors, TFII/genetics , Adult , Aged , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/pathology , Cells, Cultured , Endothelial Cells/pathology , Epithelial Cells/pathology , Female , Genome-Wide Association Study/methods , Humans , Inflammation/pathology , Male , Mice , Mice, Inbred C57BL , Middle Aged , NF-kappa B/genetics , Signal Transduction/genetics
12.
J Neurosurg Spine ; 34(6): 936-941, 2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33836499

ABSTRACT

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH)-related vertebral fractures essentially require operative treatment due to severe fracture site instability and high potential risk of posttraumatic neurological deficit. However, the optimal surgical procedure remains unclear. The purpose of this study was to assess the efficacy of posterior spinal fixation with penetrating endplate screws (PESs) for DISH-related thoracolumbar fractures. METHODS: The authors conducted a retrospective, single-center, observational study. They included data from 26 consecutive patients with DISH-related thoracolumbar fractures who were treated with posterior spinal fixation using either conventional pedicle screws (PS group, n = 8) or a combined PES technique (PES group, n = 18) between 2013 and 2019. Age, sex, BMI, bone mineral density, fracture level, use of antithrombotic drug, blood loss, operation time, fixation range, perioperative American Spinal Injury Association Impairment Scale score, implant failure, revision surgery, complications, and mortality were compared. The authors also evaluated screw loosening and bone healing on radiographs and CT scans. RESULTS: More patients had vertebral fractures in the lumbar spine in the PS group than in the PES group (3 vs 0; p = 0.019). Patients in the PES group had less blood loss (63 vs 173 ml; p = 0.048) and shorter range of fixation (5 vs 5.5 levels; p = 0.041). The screw loosening rate was significantly lower in the PES group than in the PS group (3% vs 49%; p < 0.001). CONCLUSIONS: Posterior spinal fixation using a PES technique may be an ideal surgical procedure for thoracolumbar fractures with DISH, providing more rigid and less invasive fixation than PS.

13.
Int Immunol ; 32(10): 653-662, 2020 09 30.
Article in English | MEDLINE | ID: mdl-32369831

ABSTRACT

Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.


Subject(s)
Graft Rejection/immunology , Interleukin-6/immunology , Kidney Transplantation/adverse effects , Synaptotagmins/urine , Transplantation, Homologous/adverse effects , Adult , Exosomes , Female , Humans , Male , Middle Aged , Synaptotagmins/immunology
14.
JBJS Case Connect ; 10(1): e0530, 2020.
Article in English | MEDLINE | ID: mdl-32224650

ABSTRACT

CASE: A 53-year-old woman presented with Charcot arthropathy of the shoulder joint secondary to residual sensory neuropathy of Guillain-Barré syndrome, which was accompanied by swollen shoulder and restricted range of motion of the right shoulder. We performed a reverse shoulder arthroplasty (RSA). The range of motion had improved 15 months postoperatively, and there was no postoperative complication after RSA. CONCLUSION: Clinicians should be aware that Guillain-Barré syndrome can cause Charcot arthropathy of the shoulder joint. RSA is regarded as a useful treatment, although careful follow-up is needed.


Subject(s)
Arthroplasty, Replacement, Shoulder , Guillain-Barre Syndrome/complications , Joint Diseases/etiology , Female , Humans , Joint Diseases/diagnostic imaging , Joint Diseases/surgery , Middle Aged
15.
Arthritis Rheumatol ; 72(6): 931-942, 2020 06.
Article in English | MEDLINE | ID: mdl-31785076

ABSTRACT

OBJECTIVE: We have previously reported that the coactivation of NF-κB and STAT3 in nonimmune cells, including synovial fibroblasts, enhances the expression of NF-κB target genes and plays a role in chronic inflammation and rheumatoid arthritis (RA). This study was undertaken to examine the role of NF-κB activation in chondrocytes and better understand the pathogenesis of RA. Furthermore, transmembrane protein 147 (TMEM147) was investigated as a representative NF-κB activator in chondrocytes. METHODS: Clinical samples from RA patients were analyzed by immunohistochemistry. Specimens obtained from patients with polydactyly were used as control samples. The functional contribution of chondrocytes and TMEM147 to arthritis was examined in several murine models of RA. In vitro experiments (quantitative polymerase chain reaction, RNA interference, immunoprecipitation, and confocal microscopy) were performed to investigate the mechanism of action of TMEM147 in chondrocytes. RESULTS: Samples obtained from RA patients and mouse models of RA showed coactivation of NF-κB and STAT3 in chondrocytes (P < 0.001). This coactivation induced a synergistic expression of NF-κB targets in vitro (P < 0.01). Chondrocyte-specific deletion of STAT3 significantly suppressed the development of cytokine-induced RA (P < 0.01). TMEM147 was highly expressed in chondrocytes from RA patient samples and the mouse models of RA. Gene silencing of TMEM147 or anti-TMEM147 antibody treatment inhibited the cytokine-mediated activation of NF-κB in vitro (P < 0.01) and suppressed cytokine-induced RA in vivo (P < 0.01). Mechanistically, TMEM147 molecules acted as scaffold proteins for the NF-κB complex, which included breakpoint cluster region and casein kinase 2, and enhanced NF-κB activity. CONCLUSION: These results suggest that chondrocytes play a role in the development of RA via TMEM147-mediated NF-κB activation and indicate a novel therapeutic strategy for RA.


Subject(s)
Arthritis, Rheumatoid/metabolism , Chondrocytes/physiology , Membrane Proteins/physiology , NF-kappa B/metabolism , Signal Transduction/physiology , Animals , Humans , Mice
16.
Sci Rep ; 9(1): 2353, 2019 02 20.
Article in English | MEDLINE | ID: mdl-30787395

ABSTRACT

We have reported the gateway reflex, which describes specific neural activations that regulate immune cell gateways at specific blood vessels in the central nervous system (CNS). Four types of gateway reflexes exist, all of which induce alterations in endothelial cells at specific vessels of the blood-brain barrier followed by inflammation in the CNS in the presence of CNS-autoreactive T cells. Here we report a new gateway reflex that suppresses the development of retinal inflammation by using an autoreactive T cell-mediated ocular inflammation model. Exposure to photopic light down-regulated the adrenoceptor pathway to attenuate ocular inflammation by suppressing breaching of the blood-retina barrier. Mechanistic analysis showed that exposure to photopic light down-regulates the expression of α1A-adrenoceptor (α1AAR) due to high levels of norepinephrine and epinephrine, subsequently suppressing inflammation. Surgical ablation of the superior cervical ganglion (SCG) did not negate the protective effect of photopic light, suggesting the involvement of retinal noradrenergic neurons rather than sympathetic neurons from the SCG. Blockade of α1AAR signaling under mesopic light recapitulated the protective effect of photopic light. Thus, targeting regional adrenoceptor signaling might represent a novel therapeutic strategy for autoimmune diseases including those that affect organs separated by barriers such as the CNS and eyes.


Subject(s)
Color Vision/physiology , Receptors, Adrenergic, alpha-1/metabolism , Retinitis/physiopathology , Adrenergic Agents/metabolism , Animals , Autoimmune Diseases/immunology , Autoimmunity/genetics , Autoimmunity/physiology , Blood-Brain Barrier/metabolism , Blood-Retinal Barrier/metabolism , Central Nervous System/metabolism , Endothelial Cells/metabolism , Epinephrine/metabolism , Female , Inflammation/metabolism , Light , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neurons/metabolism , Norepinephrine/metabolism , Receptors, Adrenergic/metabolism , Superior Cervical Ganglion/metabolism , T-Lymphocytes/immunology
17.
Neurochem Int ; 130: 104303, 2019 11.
Article in English | MEDLINE | ID: mdl-30273641

ABSTRACT

Neuroimmunology is a research field that intersects neuroscience and immunology, with the larger aim of gaining significant insights into the pathophysiology of chronic inflammatory diseases such as multiple sclerosis. Conventional studies in this field have so far mainly dealt with immune responses in the nervous system (i.e. neuroinflammation) or systemic immune regulation by the release of glucocorticoids. On the other hand, recently accumulating evidence has indicated bidirectional interactions between specific neural activations and local immune responses. Here we discuss one such local neuroimmune interaction, the gateway reflex. The gateway reflex represents a mechanism that translates specific neural stimulations into local inflammatory outcomes by changing the state of specific blood vessels to allow immune cells to extravasate, thus forming the gateway. Several types of gateway reflex have been identified, and each regulates distinct blood vessels to create gateways for immune cells that induce local inflammation. The gateway reflex represents a novel therapeutic strategy for neuroinflammation and is potentially applicable to other inflammatory diseases in peripheral organs.


Subject(s)
Blood Vessels/immunology , Blood-Brain Barrier/immunology , Inflammation Mediators/immunology , Neuroimmunomodulation/physiology , Reflex/physiology , Animals , Blood Vessels/metabolism , Blood-Brain Barrier/metabolism , Humans , Inflammation Mediators/metabolism , Pain/immunology , Pain/metabolism
18.
J Immunol ; 201(8): 2264-2272, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30209188

ABSTRACT

Bmi1 is a polycomb group protein and regulator that stabilizes the ubiquitination complex PRC1 in the nucleus with no evidently direct link to the NF-κB pathway. In this study, we report a novel function of Bmi1: its regulation of IκBα ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF-κB-mediated gene expression in vitro and a NF-κB-mediated mouse model of arthritis in vivo. Mechanistic analysis showed that Bmi1 associated with the SCF ubiquitination complex via its N terminus and with phosphorylation by an IKKα/ß-dependent pathway, leading to the ubiquitination of IκBα. These effects on NF-κB-related inflammation suggest Bmi1 in the SCF complex is a potential therapeutic target for various diseases and disorders, including autoimmune diseases.


Subject(s)
Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Cytoplasm/metabolism , Endothelial Cells/physiology , Multiprotein Complexes/metabolism , NF-KappaB Inhibitor alpha/metabolism , Polycomb Repressive Complex 1/metabolism , Proto-Oncogene Proteins/metabolism , SKP Cullin F-Box Protein Ligases/metabolism , Animals , Cells, Cultured , Humans , Mice , Mice, Inbred C57BL , Multiprotein Complexes/genetics , NF-kappa B/metabolism , Polycomb Repressive Complex 1/genetics , Protein Binding , Protein Stability , Proteolysis , Proto-Oncogene Proteins/genetics , RNA, Small Interfering/genetics , SKP Cullin F-Box Protein Ligases/genetics , Transcriptional Activation , Ubiquitination
19.
J Immunol ; 201(8): 2256-2263, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30201812

ABSTRACT

We recently reported that NF-κB-mediated inflammation caused by breakpoint cluster region (BCR) is dependent on the α subunit of casein kinase II (CK2α) complex. In the current study, we demonstrate that presenilin 1 (Psen1), which is a catalytic component of the γ-secretase complex and the mutations of which are known to cause familial Alzheimer disease, acts as a scaffold of the BCR-CK2α-p65 complex to induce NF-κB activation. Indeed, Psen1 deficiency in mouse endothelial cells showed a significant reduction of NF-κB p65 recruitment to target gene promoters. Conversely, Psen1 overexpression enhanced reporter activation under NF-κB responsive elements and IL-6 promoter. Furthermore, the transcription of NF-κB target genes was not inhibited by a γ-secretase inhibitor, suggesting that Psen1 regulates NF-κB activation in a manner independent of γ-secretase activity. Mechanistically, Psen1 associated with the BCR-CK2α complex, which is required for phosphorylation of p65 at serine 529. Consistently, TNF-α-induced phosphorylation of p65 at serine 529 was significantly decreased in Psen1-deficient cells. The association of the BCR-CK2α-p65 complex was perturbed in the absence of Psen1. These results suggest that Psen1 functions as a scaffold of the BCR-CK2α-p65 complex and that this signaling cascade could be a novel therapeutic target for various chronic inflammation conditions, including those in Alzheimer disease.


Subject(s)
Alzheimer Disease/genetics , Casein Kinase II/metabolism , Endothelial Cells/physiology , NF-kappa B/metabolism , Presenilin-1/genetics , Proto-Oncogene Proteins c-bcr/metabolism , Amyloid Precursor Protein Secretases/metabolism , Animals , Gene Expression Regulation , Humans , Interleukin-6/genetics , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , Presenilin-1/metabolism , Promoter Regions, Genetic/genetics , Protein Binding , Proto-Oncogene Proteins c-bcr/genetics , RNA, Small Interfering/genetics , Transcription Factor RelA/metabolism , Tumor Cells, Cultured
20.
J Spine Surg ; 4(2): 403-407, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30069535

ABSTRACT

BACKGROUND: The K-line, which is a virtual line between the midpoints of the antero-posterior canal diameter at C2 and C7, can be useful for determination of surgical procedures for cervical ossification of the posterior longitudinal ligament (OPLL). Although K-line is originally measured with plain radiogram, computed tomography multiplanar reconstruction (CT-MPR) is applied for K-line measurement by several surgeons. The purpose of the present study was to analyze whether there is a difference in K-lines obtained from radiographs of standing patients and those obtained from CT-MPR images of supine patients. METHODS: The present study included 65 patients with cervical OPLL underwent surgical treatment. We investigated the K-line (+ or -) before surgery, measured from lateral cervical spine radiographs taken in standing patients in a neutral position (X-P-based K-line) and CT-MPR mid-sagittal images obtained in supine patients (CT-based K-line). The X-P-based and CT-based K-lines were compared and differences between them were assessed. RESULTS: The-X-P-based K-line was found to be (+) in 35 patients and (-) in 30 patients. Four of 35 patients with an X-P-based K-line (11%) showed a change from K-line (+) to (-) in CT-based K-line measurements. One of 30 patients with an X-P-based K-line (3%) showed a change from (-) to (+) in CT-based measurements. CONCLUSIONS: The K-line should be measured with plain radiogram of standing patients because X-P-based K-line and CT-based K-line can be different.

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