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1.
J Neuroendovasc Ther ; 18(4): 119-125, 2024.
Article in English | MEDLINE | ID: mdl-38721617

ABSTRACT

Objective: Intraorbital dural arteriovenous fistula (IO-dAVF) is a rare condition, and treatment options vary from case to case. We report a case of transarterial embolization (TAE) for IO-dAVF. Case Presentation: A 62-year-old male complained of gradually worsening pain, hyperemia, and visual impairment in the right eye. He did not exhibit diplopia or exophthalmos. Cerebral angiography revealed an arteriovenous fistula in the right orbit. The feeding arteries were the ophthalmic artery (OphA) and the artery of the superior orbital fissure (ASOF), with the superior ophthalmic vein (SOV) as the main draining vein. The venous pathway from the SOV was not clearly visible, and considering the risk of blindness with TAE from the OphA, TAE from the ASOF was performed. Onyx 18 was selected as the liquid embolic material and injected through a microcatheter placed in the internal maxillary artery. Occlusion up to the SOV was achieved, and the shunt flow completely disappeared. Normal blood flow in the OphA was maintained, hyperemia improved, and no complications were observed. Conclusion: In cases of IO-dAVF, when transvenous embolization is difficult to perform, TAE using Onyx from the vessel of the external carotid artery system may be preferred over OphA.

2.
J Neurosurg Case Lessons ; 7(16)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38621299

ABSTRACT

BACKGROUND: In mechanical thrombectomy for tandem occlusions in vertebrobasilar stroke, distal emboli from the vertebral artery lesion should be prevented. However, no suitable embolic protection devices are currently available in the posterior circulation. Here, the authors describe the case of a vertebral artery lesion effectively treated with a closed-tip stent retriever as an embolic protection device in the posterior circulation. OBSERVATIONS: A 65-year-old male underwent mechanical thrombectomy for basilar artery occlusion, with tandem occlusion of the proximal vertebral artery. After basilar artery recanalization via the nonoccluded vertebral artery, a subsequent mechanical thrombectomy was performed for the occluded proximal vertebral artery. To prevent distal embolization of the basilar artery, an EmboTrap III stent retriever was deployed as an embolic protection device within the basilar artery to successfully capture the thrombus. LESSONS: A stent retriever with a closed-tip structure can effectively capture thrombi, making it a suitable distal embolic protection device in the posterior circulation.

3.
Sci Rep ; 14(1): 3715, 2024 02 14.
Article in English | MEDLINE | ID: mdl-38355944

ABSTRACT

Increased water intake is recommended for kidney transplant recipients; however, its efficacy remains controversial. We hypothesized that pre-existing histological findings of the allograft might modulate the impact of water intake. We retrospectively analyzed 167 adults with living-donor kidney transplants (April 2011-May 2020; median observation period, 77 months) whose baseline biopsy data were available. We compared the chronic-change group (n = 38) with the control group (n = 129) to assess the impact of self-reported daily water intake on the estimated glomerular filtration rate (eGFR). The range distribution of water intake was as follows: - 1000 ml (n = 4), 1000-1500 ml (n = 23), 1500-2000 ml (n = 64), 2000-2500 ml (n = 57), 2500-3000 ml (n = 16), and 3000 - ml (n = 3). Donor age was significantly higher in the chronic-change group. In the control group, the ΔeGFR/year increase was correlated with water intake. However, the increase in the water intake of the chronic-change group significantly decreased ΔeGFR/year (1000-1500 ml: + 1.95 ml/min/1.73 m2 and > 2000 ml: - 1.92 ml/min/1.73 m2, p = 0.014). This study suggested a potential influence of increased water intake on recipients with marginal grafts in living donor kidney transplantation.


Subject(s)
Kidney Transplantation , Humans , Adult , Living Donors , Retrospective Studies , Drinking , Kidney/pathology , Glomerular Filtration Rate , Graft Survival , Biopsy , Graft Rejection , Treatment Outcome
4.
Clin Neurol Neurosurg ; 237: 108133, 2024 02.
Article in English | MEDLINE | ID: mdl-38340428

ABSTRACT

OBJECTIVE: Although consensus has been reached regarding the use of mechanical thrombectomy for acute large anterior circulation occlusion, its effectiveness in patients with posterior circulation occlusion remains unclear. This study aimed to establish the determining factors for good clinical outcomes of mechanical thrombectomy for posterior circulation occlusion. METHODS: We extracted cases of acute large vessel occlusion (LVO) in the posterior circulation from a database comprising 536 patients who underwent mechanical thrombectomy at our hospital between April 2015 and March 2021. RESULTS: Fifty-two patients who underwent mechanical thrombectomy for LVO in the posterior circulation were identified. Five patients with simultaneous occlusion of the anterior and posterior circulation were excluded; finally, 47 patients were included in this study. The median patient age was 78 years, and 36% of the patients were women. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 31, the median posterior circulation-Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS) was 8, and the median Basilar Artery on Computed Tomography Angiography (BATMAN) score was 6. The rate of good recanalization (Thrombolysis in Cerebral Infarction scale grades 2b and 3) was 96%, and a good prognosis (modified Rankin Scale score of 0-2 at 90 days) was achieved in 19 patients (40%). The median pc-ASPECTS was significantly higher in the good prognosis group than in the poor prognosis group (10 vs. 7; p = 0.007). The median NIHSS score at presentation was significantly lower in the good prognosis group than in the poor prognosis group (17 vs. 34; p = 0.02). The median BATMAN score was significantly higher in the good prognosis group than in the poor prognosis group (8 vs. 3.5; p = 0.0002). Multivariate analysis showed that an NIHSS score ≦ 20 at presentation was the only independent factor for good prognoses. CONCLUSION: The prognosis of mechanical thrombectomy for posterior circulation LVO was better in patients with lower NIHSS scores at presentation.


Subject(s)
Stroke , Vertebrobasilar Insufficiency , United States , Humans , Female , Aged , Male , Retrospective Studies , Treatment Outcome , Vertebrobasilar Insufficiency/diagnostic imaging , Vertebrobasilar Insufficiency/surgery , Stroke/diagnostic imaging , Stroke/surgery , Thrombectomy/methods
5.
Commun Biol ; 7(1): 96, 2024 01 13.
Article in English | MEDLINE | ID: mdl-38218950

ABSTRACT

Exposure of testes to high-temperature environment results in defective spermatogenesis. Zebrafish exposed to high temperature exhibited apoptosis not only in germ cells but also in Leydig cells, as expected from studies using mice or salmon. However, the role of testicular somatic cells in spermatogenesis defects remains unclear. We found that in Leydig cells the Trpv4 gene encoding the temperature sensitive ion channel was specifically upregulated in high temperature. High temperature also reduced hormone synthesis in Leydig cells and led to a prompt downregulation of sperm motility. In the Trpv4 null mutant, neither Leydig cell-specific apoptosis nor decreased sperm motility was observed under high temperature. These results indicate that Leydig cell specific-apoptosis is induced via Trpv4 by high temperature. Notably this Trpv4-dependent mechanism was specific to Leydig cells and did not operate in germ cells. Because sperm exposed to high temperature exhibited compromised genome stability, we propose that temperature sensing leading to apoptosis in Leydig cells evolved to actively suppress generation of offspring with unstable genome.


Subject(s)
Leydig Cells , Zebrafish , Animals , Male , Mice , Apoptosis/physiology , Leydig Cells/physiology , Semen , Sperm Motility , Spermatozoa , Temperature , Zebrafish/genetics
6.
J Neurosurg ; 140(1): 172-182, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37503935

ABSTRACT

OBJECTIVE: According to benchtop studies, the oversizing of a Pipeline embolization device (PED) relative to the parent artery leads to a significant increase in porosity and potentially compromises aneurysm occlusion as well as transitional zone (TZ) formation around the neck of aneurysms. However, no clinical assessment has been reported. Here this potential was studied by measuring the dynamic changes of PEDs in the clinical time course. METHODS: The authors retrospectively examined 124 anterior circulation unruptured aneurysms in 114 consecutive patients treated with a PED between July 2015 and December 2020 at their institution. The authors excluded 77 cases of 68 patients with adjunctive coil embolization or multiple stents that could affect the PED dynamics and measurements, and 47 aneurysms in 46 patients were included. Measurements were performed before, immediately after, and 6 months after treatment, and then at intervals of 6 months to 1 year after that for nonocclusion cases. RESULTS: Complete occlusion was achieved in 79.0% and incomplete occlusion in 21.0% at last follow-up. The PED length immediately after deployment was 136% nominal length. A multivariable regression analysis revealed that age (OR 1.11/year; p = 0.02) and PED elongation from nominal length (OR 1.31/mm; p = 0.012) were independently associated with a higher rate of incomplete occlusion at the last follow-up. TZ formation did not affect the occlusion rate. CONCLUSIONS: PED elongation from the nominal length is a new predictor of incomplete aneurysm occlusion. The PED showed vascular remodeling by changing its diameter and length in the clinical course. TZ formation was remodeled and did not affect the occlusion rate.


Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm , Humans , Treatment Outcome , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Retrospective Studies , Cerebral Angiography , Follow-Up Studies
7.
Transplant Proc ; 55(4): 777-781, 2023 May.
Article in English | MEDLINE | ID: mdl-37198100

ABSTRACT

BACKGROUND: Doppler ultrasonography (US) is a noninvasive examination for assessing graft function after kidney transplantation. Although Doppler US is routinely performed, only a few reports have investigated whether a high resistive index (RI) detected by Doppler US affects graft function and survival. We hypothesized that there is a relationship between a high RI and inferior outcomes after kidney transplantation. METHODS: We included 164 living kidney transplant patients treated between April 2011 and July 2019. We divided the patients into 2 groups according to RI (cut-off, 0.7) 1 year after transplantation. RESULTS: The recipient was significantly older in the high RI (≥0.7) group. Moreover, there were significant differences in the prevalence of pretransplant diabetes mellitus and the value of pretransplant hemoglobin A1c. Regarding long-term outcome, there was no significant difference in overall graft survival (5 years, 92.6% vs 91.8%; 10 years, 85.0% vs 67.9%; P = .64). On the other hand, the mortality was significantly worse in the high RI group (5 years, 99.1% vs 93.9%; 10 years, 96.4% vs 70.0%, P = .013). CONCLUSIONS: A high RI might predict mortality after kidney transplantation.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Ultrasonography, Doppler , Vascular Resistance , Ultrasonography , Graft Survival , Kidney
8.
Interv Neuroradiol ; : 15910199231176709, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37218151

ABSTRACT

BACKGROUND: An exchange maneuver is useful for the delivery of devices to target vessels. However, hemorrhagic complications can occur due to vessel perforation during an exchange maneuver. In addition, the exchange is often challenging due to unfavorable anatomy. Center Wire is an exchange-length wire with a nondetachable stent that was developed to improve navigation and stability during exchange maneuvers. The aim of this study is to investigate the safety and efficacy of Center Wire of the anchor wire technique during neuroendovascular treatment. METHODS: Ten patients with intracranial aneurysms were treated after signing a Certified Review Board-approved consent. Anchor wire technique was used in all patients to navigate catheters to the target vessel for aneurysm treatment. RESULTS: Anchor wire technique was successfully applied in all 10 cases using Center Wire. One device-related incident of vasospasm occurred which was asymptomatic. No device-related dissection, perforation, or thromboembolic events occurred. One patient had intraoperative aneurysm rupture during coil placement which was treated immediately without clinical consequences. Two patients had postoperative ischemic strokes due to thrombotic occlusion of branches originating from the aneurysm which were unrelated to the device. CONCLUSIONS: This first-in-human trial of Center Wire demonstrated the safety and efficacy of the anchor wire technique for neuroendovascular treatment in a strictly regulated prospective registry trial.

9.
J Neurosurg ; 139(6): 1542-1551, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37178023

ABSTRACT

OBJECTIVE: In a previous study, the authors showed that the migration of Schwann cells (SCs) through end-to-side (ETS) neurorrhaphy promotes axonal regrowth within an acellular nerve graft. In the present study, the authors investigated whether a similar strategy using an artificial nerve (AN) would allow reconstruction of a long nerve gap (20 mm) in rats. METHODS: Forty-eight 8- to 12-week-old Sprague Dawley rats were divided into control (AN) and experimental (SC migration-induced AN [SCiAN]) groups. Prior to the experiment, the ANs used in the SCiAN group were populated in vivo with SCs over a 4-week period by ETS neurorrhaphy onto the sciatic nerve. In both groups, a 20-mm sciatic nerve defect was reconstructed in an end-to-end fashion using 20-mm ANs. Sections from the nerve graft and distal sciatic nerve in both groups underwent assessments at 4 weeks for SC migration by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. At 16 weeks, axonal elongation was assessed by immunohistochemical analysis, histomorphometry, and electron microscopy. The number of myelinated fibers was counted, the g-ratio was calculated, and myelin sheath thickness and axon diameter were measured. Furthermore, functional recovery was evaluated at 16 weeks using the Von Frey filament test for sensory recovery and by calculating the muscle fiber area for motor recovery. RESULTS: The area occupied by SCs at 4 weeks and by axons at 16 weeks was significantly larger in the SCiAN group than in the AN group. Histomorphometric evaluation of the distal sciatic nerve revealed a significantly greater number of axons. At 16 weeks, plantar perception in the SCiAN group was significantly better, demonstrating improvement in sensory function. However, no tibialis anterior muscle motor improvement was observed in either group. CONCLUSIONS: The induction of SC migration into an AN by ETS neurorrhaphy is a useful technique for repairing 20-mm nerve defects in rats, with better nerve regeneration and sensory recovery. No motor recovery was observed in either group; however, motor recovery might require a longer period of time than the lifespan of the AN used in this study. Future studies should investigate whether structural and material reinforcement of the AN, to lower its decomposition rate, can improve functional recovery.


Subject(s)
Myelin Sheath , Schwann Cells , Rats , Animals , Rats, Sprague-Dawley , Schwann Cells/physiology , Sciatic Nerve/surgery , Neurosurgical Procedures , Nerve Regeneration/physiology
10.
Transplant Proc ; 55(4): 748-751, 2023 May.
Article in English | MEDLINE | ID: mdl-37031039

ABSTRACT

BACKGROUND: Medication nonadherence is associated with worse graft outcomes but is hard to recognize in clinical settings due to its self-reporting nature. We hypothesized that appointment nonadherence might be associated with worse graft outcomes in living donor kidney transplantation. METHODS: We included 167 adult living-donor kidney transplants whose grafts survived >2 years from April 2011 to May 2020. Thirty-two cases of appointment nonadherence were identified and compared with the controls (n = 135). RESULTS: Younger age, male sex, higher body weight, and parent donor were significantly observed in the appointment nonadherence group. The appointment nonadherence group was significantly associated with worse graft survival (5 years: 82.3% vs 98.9%, P < .001, 10 years: 67.2% vs 89.6%, P < .001), de novo donor-specific antibody production, acute rejection, as well as the decline of graft function. Furthermore, appointment nonadherence had a 4-fold higher risk of graft loss after an adjustment with recipient age, sex, body weight, and donor type (adjusted hazard ratio: 3.93, 95% CI: 1.15-13.42, P = .029). CONCLUSIONS: Appointment nonadherence might be an alternative predictor for worse graft outcomes after living donor kidney transplantation.


Subject(s)
Kidney Transplantation , Adult , Humans , Male , Kidney Transplantation/adverse effects , Living Donors , Graft Rejection , Kidney , Graft Survival , Body Weight
11.
Heliyon ; 9(3): e14360, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36950603

ABSTRACT

Objectives: Flow diverter or stent implantation to intracranial target lesion requires large inner diameter microcatheter navigation. The exchange method using stiff long wire is often necessary if it is difficult to navigate over the regular guidewire. However, this method has an intrinsic risk of vessel damage and may cause severe complications. We investigated the safety and efficacy of a new device, the Stabilizer device for navigation in a first-in-human clinical trial under the Certified Review Board agreement. Materials and methods: The Stabilizer is a 320 cm length exchange wire with a stent for anchoring and is compatible with a 0.0165" microcatheter. The trial design is a prospective single-arm open-label registry. Inclusion criteria are elective flow diverter treatment or stent-assisted coiling, expected to be difficult to navigate a microcatheter with a regular micro guidewire, and obtained documented consent. The primary endpoint of the study was a hemorrhagic complication. Results: Five patients were enrolled in this trial. The median age is 52 years, ranges from 41 to 70, and all patients were female. Three aneurysms were located on the internal carotid artery, one on the vertebral artery, and one on the basilar artery. Basilar artery aneurysm was treated by stent-assisted coiling and others were treated by flow diverter deployment. All cases successfully navigate microcatheter for the treatment by the trial method using Stabilizer device without any adverse event. Conclusions: The results from this first-in-human consecutive five cases show the safety of the Stabilizer device in neuro-endovascular therapy for navigation of devices to the intracranial target lesion.

12.
Nat Commun ; 14(1): 1428, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36918573

ABSTRACT

Teleost fishes exhibit complex sexual characteristics in response to androgens, such as fin enlargement and courtship display. However, the molecular mechanisms underlying their evolutionary acquisition remain largely unknown. To address this question, we analyse medaka (Oryzias latipes) mutants deficient in teleost-specific androgen receptor ohnologs (ara and arb). We discovered that neither ar ohnolog was required for spermatogenesis, whilst they appear to be functionally redundant for the courtship display in males. However, both were required for reproductive success: ara for tooth enlargement and the reproductive behaviour eliciting female receptivity, arb for male-specific fin morphogenesis and sexual motivation. We further showed that differences between the two ar ohnologs in their transcription, cellular localisation of their encoded proteins, and their downstream genetic programmes could be responsible for the phenotypic diversity between the ara and arb mutants. These findings suggest that the ar ohnologs have diverged in two ways: first, through the loss of their roles in spermatogenesis and second, through gene duplication followed by functional differentiation that has likely resolved the pleiotropic roles derived from their ancestral gene. Thus, our results provide insights into how genome duplication impacts the massive diversification of sexual characteristics in the teleost lineage.


Subject(s)
Oryzias , Receptors, Androgen , Animals , Male , Female , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Fishes/genetics , Fishes/metabolism , Biological Evolution , Evolution, Molecular , Oryzias/genetics , Oryzias/metabolism
13.
J Stroke Cerebrovasc Dis ; 32(2): 106876, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36470175

ABSTRACT

A persistent primitive trigeminal artery (PPTA) is a vessel remnant of carotid-vertebrobasilar anastomosis. The aneurysm at the bifurcation of the internal carotid artery (ICA) and PPTA tends to have a broad neck with the branch incorporated into the sac. Because PPTA supplies to the posterior circulation and branches off direct pontine perforators, PPTA preservation should always be considered when treating PPTA aneurysms to avoid ischemic complications.We report a case of the wide-neck ICA-PPTA aneurysm successfully treated with the PulseRider-assisted coil embolization, resulting in complete occlusion with PPTA patency. Relevant anatomy and endovascular strategy of the PPTA aneurysms are discussed.


Subject(s)
Carotid Artery Diseases , Embolization, Therapeutic , Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Intracranial Aneurysm/complications , Embolization, Therapeutic/adverse effects , Carotid Artery, Internal/diagnostic imaging , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/therapy , Carotid Artery Diseases/complications , Basilar Artery
14.
Transpl Int ; 35: 10754, 2022.
Article in English | MEDLINE | ID: mdl-36406779

ABSTRACT

Urinary tract infection (UTI) occurs in 25% of recipients of living-donor kidney transplantation (LDKT). Female sex, age, and anatomical abnormalities have been reported as recipient-related risk factors for UTI after LDKT; few studies have reported donor-related factors. We retrospectively examined UTI occurrence within 5 years of transplantation in recipients (n = 211) who underwent LDKT at our hospital between April 2011 and April 2021. All nephrectomies were performed using a retroperitoneal pure laparoscopic approach. The ureter was dissected at the lower level of the common iliac artery and trimmed to the shortest length, enough to reach the bladder using extra vesicular ureterocystoneostomy with a 3 cm submucosal tunnel. Twenty-nine recipients (13.7%) developed UTI within 5 years, and the median time to onset was 40.0 days. After adjusting for the well-known factors, including recipient sex, graft ureter length was an independent factor for UTI occurrence (HR 1.25, 95% CI 1.02∼1.53, p = 0.028) in the multivariate Cox regression analysis. The long ureter is usually trimmed, and the widest part is used for anastomosis, which may increase the possibility of reflux from the bladder to the ureter in the standard technique. The ureter length may be associated with the incidence of UTI after LDKT.


Subject(s)
Kidney Transplantation , Ureter , Urinary Tract Infections , Humans , Female , Ureter/surgery , Living Donors , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Retrospective Studies , Urinary Tract Infections/etiology , Urinary Tract Infections/epidemiology
15.
Life Sci Alliance ; 5(10)2022 10.
Article in English | MEDLINE | ID: mdl-35961782

ABSTRACT

Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood-nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD. Abundant neutrophil extracellular traps (NETs) were formed around neutrophils, and its inhibition dramatically increased macrophage infiltration into the parenchyma. Furthermore, inhibition of either MIF or its receptor, CXCR4, in neutrophils decreased NET formation, resulting in enhanced macrophage infiltration into the parenchyma. Moreover, inhibiting MIF for just 2 h after peripheral nerve injury promoted the repair process. These findings indicate that neutrophils delay the repair process in WD from outside the parenchyma by inhibiting macrophage infiltration via NET formation and that neutrophils, NETs, MIF, and CXCR4 are therapeutic targets for peripheral nerve regeneration.


Subject(s)
Extracellular Traps , Peripheral Nerve Injuries , Extracellular Traps/physiology , Humans , Macrophages/physiology , Neutrophils , Peripheral Nerve Injuries/pathology , Wallerian Degeneration/pathology
16.
J Immunother Cancer ; 10(7)2022 07.
Article in English | MEDLINE | ID: mdl-35793868

ABSTRACT

BACKGROUND: Understanding the mechanisms of non-T cell inflamed tumor microenvironment (TME) and their modulation are important to improve cancer immunotherapies such as immune checkpoint inhibitors. The involvement of various immunometabolisms has recently been indicated in the formation of immunosuppressive TME. In this study, we investigated the immunological roles of stearoyl-CoA desaturase 1 (SCD1), which is essential for fatty acid metabolism, in the cancer immune response. METHODS: We investigated the roles of SCD1 by inhibition with the chemical inhibitor or genetic manipulation in antitumor T cell responses and the therapeutic effect of anti-programmed cell death protein 1 (anti-PD-1) antibody using various mouse tumor models, and their cellular and molecular mechanisms. The roles of SCD1 in human cancers were also investigated by gene expression analyses of colon cancer tissues and by evaluating the related free fatty acids in sera obtained from patients with non-small cell lung cancer who were treated with anti-PD-1 antibody. RESULTS: Systemic administration of a SCD1 inhibitor in mouse tumor models enhanced production of CCL4 by cancer cells through reduction of Wnt/ß-catenin signaling and by CD8+ effector T cells through reduction of endoplasmic reticulum stress. It in turn promoted recruitment of dendritic cells (DCs) into the tumors and enhanced the subsequent induction and tumor accumulation of antitumor CD8+ T cells. SCD1 inhibitor was also found to directly stimulate DCs and CD8+ T cells. Administration of SCD1 inhibitor or SCD1 knockout in mice synergized with an anti-PD-1 antibody for its antitumor effects in mouse tumor models. High SCD1 expression was observed in one of the non-T cell-inflamed subtypes in human colon cancer, and serum SCD1 related fatty acids were correlated with response rates and prognosis of patients with non-small lung cancer following anti-PD-1 antibody treatment. CONCLUSIONS: SCD1 expressed in cancer cells and immune cells causes immunoresistant conditions, and its inhibition augments antitumor T cells and therapeutic effects of anti-PD-1 antibody. Therefore, SCD1 is an attractive target for the development of new diagnostic and therapeutic strategies to improve current cancer immunotherapies including immune checkpoint inhibitors.


Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Non-Small-Cell Lung , Colonic Neoplasms , Lung Neoplasms , Stearoyl-CoA Desaturase , Animals , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/immunology , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Mice , Mice, Knockout , Stearoyl-CoA Desaturase/antagonists & inhibitors , Stearoyl-CoA Desaturase/immunology , Tumor Microenvironment , Wnt Signaling Pathway/immunology , beta Catenin/immunology
17.
Cell Mol Life Sci ; 79(6): 289, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35536429

ABSTRACT

Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.


Subject(s)
Peripheral Nerve Injuries , Urokinase-Type Plasminogen Activator , Axons/physiology , Humans , Interleukin-4/pharmacology , Macrophages/physiology , Nerve Regeneration/physiology , Peripheral Nerve Injuries/therapy , Receptors, Urokinase Plasminogen Activator/genetics
18.
Int J Surg Case Rep ; 92: 106869, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35231738

ABSTRACT

INTRODUCTION AND IMPORTANCE: Extensor pollicis longus (EPL) tendon injury is a major complication in distal radial fracture repair. The risk factors for EPL tendon injury are prominent dorsal screws, direct intraoperative damage through drilling, and/or dorsal roof fragments. Herein, we introduce a simple technique to minimize the risk of EPL tendon rupture after volar plate fixation of distal radial fracture. CASE PRESENTATION: The patient was a 67-year-old woman with an intra-articular unstable distal radial fracture treated by volar locking plate fixation. Intraoperatively, we opened the third compartment after screw fixation. Because the screw had penetrated the floor of the third compartment, we moved the EPL tendon out of its groove and closed the third compartment by suturing the retinaculum. We confirmed that the EPL tendon was intact 7 years postoperatively, even though the screw was prominent in the third compartment. CLINICAL DISCUSSION: After volar plate fixation of the distal radial fracture, we partially open the third compartment through an approximately 2-cm-long incision on the ulnar side of Lister's tubercle. If the screw is prominent in the third compartment, we completely open the third compartment, take the EPL tendon out of its groove, and close the compartment by suturing the retinaculum. Our method was proved useful because the EPL tendon has remained intact for 7 years with the screw protruding into the third compartment. CONCLUSION: Our surgical technique is useful to prevent secondary EPL tendon rupture after distal radial plate fixation.

19.
Neurosurg Rev ; 45(3): 2221-2230, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35066661

ABSTRACT

In the treatment of an intracranial aneurysm with the flow diverter, the combined use of coil embolization can help promote subsequent progressive thrombosis within the aneurysm sac and reduce the risk of delayed aneurysm rupture. This study retrospectively reviewed outcomes of patients who had undergone the Pipeline Embolization Device (PED) with adjunctive coil embolization (PED/coil) at a single center to determine its safety and efficiency. Patients with internal carotid artery aneurysms following an intradural component were selected for PED/coil between 2015 and 2020. All patients were premedicated with dual antiplatelet therapy of aspirin plus clopidogrel or prasugrel. A minimal number of PEDs were deployed, with coils inserted using a stent-jail technique, avoiding dense packing. A total of 46 aneurysms (43 patients; median dome size, 11.6 mm; median neck width, 6.3 mm) were treated with PED/coil. The median volume embolization ratio was 14.8%. The degree of angiographic filling at the 6-month and latest angiography showed complete occlusion in 60.5% (26/43) and 70.5% (31/44), respectively. Small (< 10 mm) aneurysms achieved a higher complete occlusion rate in the early period; a lower cumulative incidence of aneurysm occlusion was observed in large and giant (≥ 10 mm) aneurysms (P = .024). The median clinical follow-up was 22 months, and no aneurysm ruptures occurred. Favorable clinical outcomes were achieved, with permanent neurological morbidity of 4.7% and no mortality. PED/coil demonstrated a high angiographic occlusion rate at an early stage. Loosely packed coils are sufficient to obliterate aneurysms effectively.


Subject(s)
Aneurysm, Ruptured , Carotid Artery Diseases , Embolization, Therapeutic , Intracranial Aneurysm , Aneurysm, Ruptured/etiology , Carotid Artery Diseases/etiology , Carotid Artery, Internal/surgery , Cerebral Angiography , Embolization, Therapeutic/methods , Follow-Up Studies , Humans , Intracranial Aneurysm/etiology , Intracranial Aneurysm/surgery , Japan/epidemiology , Retrospective Studies , Stents , Treatment Outcome
20.
JMA J ; 4(3): 207-215, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34414314

ABSTRACT

Autophagy is a major intracellular degradation system and plays important roles in various physiological processes such as metabolic adaptation and intracellular homeostasis. It degrades intracellular components both randomly and selectively. Autophagic activity is tightly regulated primarily by nutrient availability, but also by other extracellular and intracellular signals. Growing evidence suggests that there are multiple links between autophagy and the primary cilium. The primary cilium is an organelle present on the cell surface and is important for keeping cellular integrity by transducing extracellular stimuli inside the cell. Recent studies have revealed that autophagy selectively degrades the ciliogenesis inhibitory proteins OFD1 and MYH9, promoting ciliogenesis. Conversely, autophagy also inhibits ciliogenesis under growth conditions. The primary cilium can also regulate autophagic activity. These findings suggest that the relationship between autophagy and the primary cilia is bidirectional, and that both are important for maintaining the normal function of various organs.

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